Physical environments play important roles for maturation of mechanical functions of tissue. In this study, effects of relative tribological movement on the expression of tribological function of regenerated synovial membrane were investigated. Fibroin sponge derived from silk was used as a three-dimension scaffold for the synovial membrane regeneration. Synovial cells were isolated from human synovial membrane, and were seeded onto the fibroin sponge. Magnetic stirring system (named Stirring Chamber) was used for culturing with relative slip motion where the cell-seeded side of the scaffold had been rubbed by a glass culture dish for 24 hours/day. Histological view of regenerated tissue of the dynamically cultured group (D group) showed extracellular-matrix-like eosinophilic meshwork structure formed continuously on the meshwork structure of the fibroin sponge. The newly formed tissue showed expression of collagen type I, especially on the surface of fibroin sponge. These structures were not seen in the statically incubated group (S group). Each group didn’t show expression of collagen type II. Frictional force was measured by using leaf spring method under the conditions of the sliding velocity: 0.8 mm/s, the loading time prior to sliding: 1 minute, and the applied load during the experiment: 0.029 N. The counterface for regenerated synovium was a flat stainless steel of which roughness was 0.06 μm Ra. All frictional experiments were performed in the saline solution and at room temperature (25°C). The friction coefficient of tissues cultured statically was 0.6–0.8, and that of tissues cultured with sliding motion was 0.2–0.4 at one week culturing, 0.3–0.5 at two weeks culturing. Our previous experiment showed that combination of fibroin-sponge scaffold and Stirring-chamber culturing system improved the tribological performance of regenerated cartilage tissue. The present study suggests that this combination have also a possibility for synovial cells to form functional lubricious membrane which can be used as anti-adhesion membrane for knee, ligament, and/or other surgical procedures. However, the deterioration of lubrication properties in the 2 weeks dynamically cultured group would indicate that the too long continuous tribological movement does not provide an optimal condition. More fine tribological loading history should be designed

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future

In the context of regenerative medicine for the treatment of musculoskeletal pathologies mesenchymal stromal cells (MSCs) have shown good results thanks to secretion of therapeutic factors, both free and conveyed within the extracellular vesicles (EV), which in their totality constitute the “secretome”. The portfolio and biological activity of these molecules can be modulated by both in vitro and in vivo conditions, thus making the analysis of these activities very complex. A deep knowledge of the targets regulated by the secretome has become a matter of fundamental importance and a homogeneous and complete molecular characterization is still lacking in the field of applications for the musculoskeletal system. Therefore, the aim of this work was to characterize the secretome obtained from adipose-derived MSCs (ASCs), and its modulation after pre-conditioning of the ASCs. Pre-conditioning was done by culturing cells in the presence of i) high levels of IFNγ, as proposed for the production of clinical grade secretome with enhanced regenerative potential, ii) low levels of inflammatory stimuli, mimicking conditions found in the osteoarthritis (OA) synovial fluid. Furthermore, EVs ability to migrate within cartilage, chondrocyte and synoviocytes obtained from OA patients was evaluated. The data showed that more than 50 cytokines / chemokines and more than 200 EV-microRNAs are detectable at various intensity levels in ASCs secretomes. The majority of the most abundantly present molecules are involved in the remodelling of the extracellular matrix and in the homeostasis and chemotaxis of inflammatory cells including macrophages, which in OA are often characterized by an M1 inflammatory polarization, promoting their transition to an M2 anti-inflammatory phenotype. Inflammatory priming with IFNγ and synovial fluid-like conditions were able to further increase the ability of the secretome to interact with inflammatory cells and modulate their migration. Finally, the penetration of the EVs in the cartilage explants resulted a rapid process, which begins a few minutes after administration of the EVs that are able to reach a depth of 30-40 μm in 5 hours. The same capacity for interaction was also verified in chondrocytes and synoviocytes isolated from the cartilage and synovial membrane of OA patients. Thanks to the soluble factors and EV-microRNAs, the ASCs secretome has shown a strong propensity to modulate the inflammatory and degenerative processes that characterize OA. The inflammatory pre-conditioning through high concentrations of inflammatory molecules or in conditions similar to the synovial fluid of OA patients was able to increase this capacity by increasing their chemotactic power. The microscopy data also support the hypothesis of the ability of MSC-EVs to influence the chondrocytes residing in the ECM of the cartilage and the synovial cells of the synovial membrane through active interaction and the release of their therapeutic content

Inflammatory changes in synovial tissues occur commonly in knee osteoarthritis (OA) and are termed “inflammatory OA”. The pathogenic significance of this inflammatory OA is uncertain. It is also not known whether inflammatory changes in the synovial membrane are reflected in the synovial fluid (SF) and whether the SF contains a similar inflammatory cell infiltrate. This study examined 34 cases of knee joint OA and cytologically and immunohistochemically characterised inflammatory cells in the synovial membrane and SF. Specimens of SF and synovial membrane were taken at the time of knee arthroplasty. All cases of inflammatory OA synovium contained (CD68+) macrophages; several cases also contained a scattered, focally heavy (CD3+) lymphocytic infiltrate and occasional lymphoid aggregates. Inflammatory changes in OA SF reflected this cell composition with numerous CD68+ macrophages and CD3+ lymphocytes being noted in inflammatory OA cases. The SF volume was greater (> 5ml) in cases of inflammatory OA. Non-inflammatory OA knee joints contained very few inflammatory cells, which were mainly macrophages, in both the synovial membrane and SF. Our findings indicate that inflammatory changes in the synovial membrane of OA knee joints are reflected in the SF and that the volume of SF is commonly increased in cases of inflammatory OA. Both macrophages and lymphocytes in the inflammatory infiltrate of knee joint SF may contribute to joint destruction in OA by providing mononuclear phagocyte osteoclast precursors and the production of inflammatory cytokines and growth factors that promote osteoclastogenesis. In conclusion, the cytology of SF and synovitic membrane are similar in inflammatory OA. With knee effusions of greater than 5mls and inflammatory synovitic membrane consideration of total knee arthoplasty in the presence of single compartment disease should be considered because of the risk of further joint destruction

Background. Tenosynovial giant cell tumour (TGCT) is a benign proliferative disease affecting synovial membranes. There are two forms, localised and diffuse, which although histologically similar are managed differently. It is locally invasive and is treated in most cases by operative excision. The aim of this study was to assess outcomes from the largest single-centre experience to date in patients with this condition. Methods. A retrospective analysis of 123 cases was performed in patients treated between 2003 and 2019 with TGCT of the foot and/or ankle. Data was collected on age at presentation, radiological pattern of disease, location of disease, treatment provided and recurrence rates. The minimum follow-up was 2 years with a mean of 7.7 years. Results. 47 male and 76 female patients with a mean age at diagnosis of 39 (range, 11–76) years were identified. 85 (69.1%) cases were categorised as localised and 38 (30.9%) were diffuse. Half of the cases presented in the ankle (62/123, 50.4%). 89% (110) of patients underwent open operative excision of the lesion. Radiotherapy was used in 2 cases for recurrent disease. Pain was the most common postoperative symptom which developed in 20% (22/110) of cases). 13 cases were managed nonoperatively where symptoms were minimal, with one case requiring surgery at a later date. Disease recurrence was 3.5% (3/85) in localised disease and 36.8% (14/38) in diffuse disease giving an overall recurrence rate of 13.8% (17/123). Conclusion. The outcomes of TGCT management are dependent on the type of disease, the extent of preoperative erosive changes and the presence of pre-operative pain. We present a summary of recommended management based on the experience from this single tertiary centre

Articular invasion by malignant bone tumours around the knee is one of the most important criterions to determine prior surgery. MR imaging is the most accurate exam in staging bone sarcomas. Although, past studies showed that when MRI shows evidence of intra articular involvement by tumour, the incidence of false positive diagnosis and subsequent excessively radical surgery is as high as 50%. The aim of this study is to determine growth pattern of bone sarcomas into the joint in order to assess which are the limits of the joint compartment. We reviewed retrospectively 18 cases of primary intra medullary sarcomas with epiphyseal extension located around the knee. The tumour was located in the distal femur in 11 cases and in the proximal tibia in 7 cases. In tumours located in the distal femur, two distinct modes of extension towards synovium and joint space were identified. The most common pattern was tumour growth along the anterior and intra articular part of the distal femur. This pattern was observed in 10 cases. The tumour displaced anteriorly soft tissues and remained extra synovial in 6 cases. Only in 4 cases, tumour contaminated the joint space. The extension was in all cases marginally close to the cartilage of the trochlea in the transitional zone between cartilage and synovial membrane. The second pattern was extension through the inter condylar notch which was observed in three cases. Growth was around the osseous-tendinous junction of the cruciate ligaments and never within the ligament. In tumors in the proximal tibia, although tumour was close to the osteochondral junction, cartilage was not breached anyway. Tumour got around the cartilage. Extension of the tumour to the articular joint was marginally under the posterior capsule insertions making contact with the edge of the articular cartilage. This pattern was observed in two cases. We didn’t observe an erosion of cartilage layer, in the limits of the sections done. Our study, demonstrated that cartilage and synovial membrane, since they are not breached, represent reliable margins for intra articular resections. We identified in the current study, one mode of tumour extension towards synovium and joint space. In all cases, extension was in junctional zones between cartilage and synovial membrane or cartilage and articular capsule. The articular cartilage was the most resistant barrier, having no vascular perforations and probably an intrinsic resistance to tumour

Arthrofibrosis is a relatively frequent complication after total knee arthroplasty. Although stiffness after total hip arthroplasty (THA), because of formation of heterotopic ossification or other causes, is not uncommon, to the authors’ best knowledge, arthrofibrosis after THA has not been described. The aim of this study is to describe the arthrofibrosis of the hip after primary total hip arthroplasty using an established clinical and histological classification of arthrofibrosis. We retrospectively examined all patients who were histologically confirmed to have arthrofibrosis after primary THA during revision surgery by examination of tissue samples in our clinic. Arthrofibrosis was diagnosed according to the histopathological SLIM-consensus classification, which defines seven different SLIM types of the periimplant synovial membrane. The SLIM type V determines the diagnosis of endoprosthesis-associated arthrofibrosis. The study population consists of 66 patients who were revised due to arthrofibrosis after primary THA. All patients had a limitation in range of motion prior to revision with a mean flexion of 90° (range from 40 to 125), mean internal rotation of 10° (range from 0 to 40) and mean external rotation of 20° (range from 0 to 50). All patients had histological SLIM type V arthrofibrosis, corresponding to endoprosthesis-associated arthrofibrosis. Histological examination revealed that seven patients (10.6%) had particle-induced and 59 patients (89.4%) had non-particle-induced arthrofibrosis. This is the first decription of endoprosthetic-associated arthrofibrosis after primary THA on the basis of a well-established histological classification. Our study results could enable new therapeutic and diagnostic opportunities in patients with such an arthrofibrosis. Surgeons should keep arthrofibrosis as a possible cause for stiffness and pain after primary total hip arthroplasty in mind. Level of evidence Diagnostic study, Level of Evidence IV. Thorsten Gehrke and Lara Althaus contributed equally to the writing of this manuscript

Introduction. Metal on metal bearings are used especially in hip resurfacing. On the one hand, small bone preserving implants can be used. On the other hand recent studies found a variety of local and systemic side effects, for instance the appearance of pseudotumors, that are explained by pathologic biological reaction of the metal wear debris. The detailed mechanisms are still not understood until now. Thus it was the aim of this study to investigate the local reaction of metal wear particles and metal ions in a murine model. The hypothesis was that mainly metal ions provoke adverse histopathological reactions in vivo. Material and Methods. Three groups, each with 10 Balb / c mice were generated. Group A: injection of a 50 µl metal ion suspension at a concentration of 200 µg / l in the left knee. Group B: injection of a 50 µl 0,1 vol% metal particle suspension into the left knee joint. Group C (control group): injection of a 50 µl of 0,1 vol% PBS-suspension in the left knee. Incubation for 7 days, followed by euthanasia of the animals by intracardiac pentobarbital. The left and right knee, the lungs, kidneys, liver and spleen were removed. Histologic paraffin sections in 2 microns thickness were made, followed by HE (overview staining) and Movat (Pentachrom staining) staining. The histologic analysis was a done by a light microscopic evaluation of the subdivided visual fields at 200× magnification. Results. In the metal ions group compared with the control group an increasing thickness of synovial membrane as a sign of an inflammatory process was detected. Cartilage and subchondral bone as well as the adjacent bone marrow remain largely unchanged. In the metal particle group a thickenend synovial membrane was found and chondral, bone and periarticular tissue necrosis. In addition, pseudotumors with a complete destruction of the femoral or tibial bone were found. Conclusion. The initial hypothesis has to be rejected. it can be postulated that the metal ions have a certain inflammatory and destructive activity, but in the end it is the metal wear particles that lead to adverse tissue necrosis and to osteolytic destructions associated with a pseudotumor genesis

INTRODUCTION:. To avoid the early onset of osteoarthritis after partial meniscectomy an effective replacement of injured meniscal tissue would be desirable. The present study investigates the behaviour of a new silk derived scaffold supplied by Orthox Ltd. (Abingdon, UK) in an in vivo sheep model. METHODS:. The scaffolds where derived from silk fibres by processing into an open porous matrix. Nine sheep (4 ± 1 years) underwent partial meniscectomy at the anterior horn of the medial meniscus followed by implantation of a scaffold. The unoperated contralateral stifle joint served as control. After six months the animals were sacrificed and the joints inspected for inflammation. The Young's modulus of the tibial cartilage, meniscus and scaffold was determined by indentation or confined compression tests. All tissues were fixed in formaldehyde for histology. The data were analysed by a Wilcoxon and Mann-Whitney-U-test. RESULTS:. The sheep were free of lameness 4 days p.o. The macroscopic analysis of the genual region and of the synovial membrane showed no signs of inflammation. This was confirmed by histological sections of synovial membrane, meniscus and scaffold. In histology, amorphous material, some fibroblast-like cell clusters and connective tissue formation was visible inside the pores of the scaffold. There were no statistically significant differences between the Young's moduli of the three measuring points in the operated and unoperated stifle joints. The meniscal tissue showed a higher modulus than the scaffolds. The scaffold's modulus significantly increased after three months implantation. DISCUSSION & CONCLUSIONS:. The presented silk scaffold withstood the loads occurring during the six months implantation period. It showed promising properties concerning biocompatibility and cartilage protection and its mechanical properties started to approach those of meniscal tissue

INTRODUCTION:. One common surgical treatment of even early OA is the implantation of a Total Joint Arthroplasty. In case of younger patients this procedure is questionable. The present study investigates the behaviour of a new silk derived scaffold supplied by Orthox Ltd. (Abingdon, UK) in an in vivo sheep model. This scaffold allows replacing the damaged areas with a resurfacing technique and will avoid the implantation of a total joint in cases of early OA. METHODS:. The scaffolds where derived from silk fibres by processing into a composite of an open porous matrix in combination with a fibres mash with the same material and covered with a smooth surface. During the process the fluid silk can be casted in any shape. Eight sheep (4 ± 1 years) underwent a surgery where a large defect (2×1 cm) was created in the weight bearing zone of the medial condylus followed by implantation of a scaffold. The unoperated contra lateral stifle joint served as control. After six months the animals were sacrificed and the joints inspected for inflammation. The Young's modulus of the cartilage and scaffold was determined by indentation or confined compression tests. All tissues were fixed in formaldehyde for histology. The data were analysed by a Wilcoxon and Mann-Whitney-U-test. The roughness of the smooth surface was measured. Synovial fluid was harvested by punction before opening the joint and analysed for particle wear debris and for any signs of inflammation. RESULTS:. The sheep were free of lameness between the 2. nd. and latest the 4th days p.o. The macroscopic analysis of the genual region and the synovial membrane showed no signs of inflammation. The findings were confirmed by histological sections of synovial membrane and scaffold. In histology, amorphous material fibroblast-like cell clusters and connective bone tissue formation was visible inside the pores of the scaffold. The scaffols were complety integrated into the underlying bone. Synovial fluid showed no signs of inflammation only the IL6 level was slightly increased. No wear particles were found. No defetcs or mayor damage of the oponend cartilage were present. The measured roughness was between 13–18 nm. DISCUSSION & CONCLUSIONS:. The presented silk scaffold withstood the loads occurring during the six months implantation period. It showed very promising properties concerning biocompatibility and cartilage protection Its mechanical properties were simmilar of those of the surrounding cartilage. Since the material can be casted into any shape it offers a wide potential use in any large joint of the human body. The production of real patient specific implants will be easy to achieve

Metallosis is a combined chemical and toxic reaction which, if the wear of a metal implant is large, may cause extensive reaction of synovial membrane and thus triggering the loosening. We present a case of a 72 year-old man, who underwent to a cemented unicompartimental porous metal coated knee implant because affected by rheumatoid arthritis complicated by osteonecrosis of medial femoral condyle of the knee. Four years after replacement, the patient presented symptoms included moderate swelling, pain, synovitis inability to bear full weight as well as grinding; plain radiographs shows well fixed implant and not finding of loosening of prosthesis; arthroscopy revealed the diagnosis of metallosis. The specimens of synovial tissue were prepared to observation to light and electron microscopy. Total synovialectomy and revison with total knee replacement were successful in relieving the symptoms. Arthroscopy examination revealed a posterior break of tibial component, source of the release of multiple metal beads; we observe alsogray black discoloration of hypertofic and hyperplastic synovium pannus like; metal beads were detected in the joint space soft tissue and were also embedded in the articulating surface of the tibia component. Microscopic examination shows metal debris as black aggregates and a diffuse sheet like proliferation inside histiocytes of villous membrane. Ultrastructural study demonstrate that the presence of metallic fragments, measuring less than 0.3 micron in diameter is predominantly concentrated inside the macrophage’s phagolisosomes. Delivery of large number of metal beads from implant and the release of smallest size metal debris play a pivotal role in the development of a foreign body granulomatous reaction. The failure of unicompartimental prosthesis has been accellerated by unperformed sinoviectomy during the first implant; the cells of synovial membrane are continuosly activated, by wear of implant material, to phagocitate and to secrete inflammatory response

Purpose: The purpose of our tissue engineering work was to produce a substitute for the anterior cruciate ligament (ACL) in laboratory cultures for human implantation and to conduct fundamental studies on healing mechanisms. Material: We used cells isolated from ACL biopsies obtained from the host, type I bovine collagen, and two bone blocks to produce ACL in culture. Methods: Several layers of collagen containing host autologous ACL cells were superposed and linked to two bones that were placed on either side, according to a process currently being patented. The cells, or fibroblasts, enter into contact with the collagen matrix and start remodelling it, in the laboratory, before implantation. This ACL produced by tissue engineering can be ready for implantation 10–12 days after isolating the autologous cells from a ruptured ACL. Results: Implantation of autologous ACL reconstructs was successful in eight goats. Histological analysis of the implanted grafts showed permanent integration into the tissues after 1–13 months. Th synovial membrane was reformed and rapidly vascularised, about one month after the graft. Thereafter, remodelling of the collagen matrix led to the formation of a very dense network of fibres, organised in bundles, very comparable to the normal histological aspect of the ACL. The bone blocks were also integrated by incorporation into the femur and tibia of the host. Sharpey fibres were present at the bone-ligament surface and a well structured fibro-cartilage was observed. In addition, the synovial membrane around the graft was innervated five months after implantation, suggesting that propioception could be recovered over time. Finally, progressive gain in force reached 20 – 36% of the normal ACL, 9 to 13 months after implantation;. Discussion: These promising data demonstrate that an autologous ACL with an interesting potential for regeneration can be produced in the laboratory, avoiding the risk of rejection and sparing healthy knee structures, thus favouring more rapid functional rehabilitation. Conclusion: Tissue engineering is a new avenue of research with potential applications in orthopaedic surgery, particularly for reconstruction of the ACL

Previous study reported that intra-articular injection of MgSO4 could alleviate pain related behaviors in a collagenase induced OA model in rats. It provided us a good description on the potential of Mg2+ in OA treatment. However, the specific efficiency of Mg2+ on OA needs to be further explored and confirmed. The underlying mechanisms should be elucidated as well. Increasing attention has been paid on existence of synovial fluid MSCs (SF-MSCs) (not culture expanded) which may participate in endogenous reparative capabilities of the joint. On the other hand, previous studies demonstrated that Mg2+ not only promoted the expression of integrins but also enhanced the strength of fibronectin-integrin bonds that indicated the promotive effect of Mg2+ on cell adhesion, moreover, Mg2+ was proved could enhance chondrogenic differentiation of synovial membrane derived MSCs by modulating integrins. Based on these evidence, we hypothesize herein intra-articular injection of Mg2+ can attenuate cartilage degeneration in OA rat through modulating the biological behavior of SF-MSCs. Human and rat SF-MSCs were collected after obtaining Experimental Ethics approval. The biological behaviors of both human and rat SF-MSCs including multiple differentiation, adhesion, colony forming, proliferation, etc. were determined in vitro in presence or absence of Mg2+ (10 mmol/L). Male SD rats (body weight: 450–500 g) were used to establish anterior cruciate ligament transection and partial medial meniscectomy (ACLT+PMM) OA models. The rats received ACLT+PMM were randomly divided into saline (control) group and MgCl2 (0.5 mol/L) group (n=6 per group). Intra-articular injection was performed on week 4 post-operation, twice per week for two weeks. Knee samples were harvested on week 2, 4, 8, 12 and 16 after injection for histological analysis for assessing the progression of OA. On week 2 and 4 after injection, the rat SF-MSCs were also isolated before the rats were sacrificed for assessing the abilities of chondrogenic differentiation, colony forming and adhesion in vitro. Statistical analysis was done using Graphpad Prism 6.01. Unpaired t test was used to compare the difference between groups. Significant difference was determined at P < 0 .05. The adhesion and chondrogenic differentiation ability of both human and rat SF-MSCs were significantly enhanced by Mg2+ (10 mmol/L) supplementation in vitro. However, no significant effects of Mg2+ (10 mmol/L) on the osteogenic and adipogenic differentiation as well as the colony forming and proliferation. In the animal study, histological analysis by Saffranin O and Toluidine Blue indicated the cartilage degeneration was significantly alleviated by intra-articular injection of Mg2+, in addition, the expression of Col2 in cartilage was also increased in MgCl2 group with respect to control group indicated by immunohistochemistry. Moreover, the OARSI scoring was decreased in MgCl2 group as well. Histological analysis and RT-qPCR indicated that the chondrogenic differentiation of SF-MSCs isolated from Mg2+ treated rats were significantly enhanced compare to control group. In the current study, we have provided direct evidence supporting that Mg2+ attenuated the progression of OA. Except for the effect of Mg2+ on preventing cartilage degeneration had been demonstrated in this study, for the first time, we demonstrated the promoting effect of Mg2+ on adhesion and chondrogenic differentiation of endogenous SF-MSCs within knee joint that may favorite cartilage repair. We have confirmed that the anti-osteoarthritic effect of Mg2+ involves the multiple actions which refer to prevent cartilage degeneration plus enhance the adhesion and chondrogenic differentiation of SF-MSCs in knee joint to attenuate the progression of OA. These multiple actions of Mg2+ may be more advantage than traditional products. Besides, this simple, widely available and inexpensive administration of Mg2+ has the potential on reducing the massive heath economic burden of OA. However, the current data just provided a very basic concept, the exact functions and underlying mechanisms of Mg2+ on attenuating OA progression still need to be further explored both in vitro and in vivo. Formula of Mg2+ containing solution also need to be optimized, for example, a sustained and controlled release delivery system need to be developed for improving the long-term efficacy

Introduction. Osteoarthritis (OA) of the knee, a prevalently degenerative joint disorder provoked by articular cartilage loss, accounts for the leading cause of total knee arthroplasty. Autophagy is an indispensable intracellular event that maintains chondrocyte survival and metabolism. MicroRNAs are non-coding small RNAs participating in tissue morphogenesis, remodeling, and homeostasis. This study was undertaken to investigate the effect of microRNA-128 (miR-128) knockdown on the development of OA knees. Materials/Methods. Knee joints in rats were subjected to anterior cruciate ligament transection (ACLT) for inducing OA. Articular cartilage, synovium, and subchondral bone microarchitecture were assessed by OARSI scoring system, histomorphometry, and μCT imaging. Chondrocyte autophagy in terms of the expression of autophagic markers Atg4, Atg12, microtubule-associated protein 1 light chain 3 (LC3), and autophagosome formation was verified. Expression of microRNA, mRNA and signaling transduction were quantified with in situ hybridization, RT- quantitative PCR, and immunoblotting. Results. Chondrocytes in the affected knees showed weak expression of autophagic markers Atg4, Atg12, and LC3-II abundances in conjunction with significant increases in OARSI scores and a 2.5-fold elevation in miR-128 expression. The gain of miR-128 signaling in intact joints through intra-articular injection of miR-128 precursor resulted in 1.8–2.1-fold elevations in serum cartilage breakdown products CTX-II and COMP concentrations. miR-128 overexpression caused the joints to show evident chondrocyte apoptosis as evidenced by TUNEL staining concomitant with severe cartilage damage. Of note, antisense oligonucleotide knockdown of miR-128 (miR-128-AS) enabled the affected knee joints to show minor responses to the ACLT escalation of autophagy dysfunction in chondrocytes, cartilage breakdown histopathology, and OARSI scores. Administration with miR-128-AS also attenuated the ACLT-induced synovial membrane thickening, hyper-angiogenesis, and hypercellularity, which subsequently alleviated osteophyte accumulation, subchondral plate destruction, and trabecular microstructure loss. Conclusion. miR-128 signaling impairs chondrocyte autophagy, which ramps up chondrocyte apoptosis and OA knee development. This study highlights an emerging miR-128 knockdown strategy that sustains cartilage microarchitecture integrity and thereby delays OA knee pathogenesis

There is currently no cure for osteoarthritis (OA), although there are ways to manage it, but most require quite invasive surgeries. There is a resident mesenchymal progenitor cell (MPC) population within the synovial membrane of the joint that have the ability to differentiate into bone, fat, and cartilage. We hypothesise that in vivo and in vitro cell surface marker expression comparisons of the MPCs can determine which population has the highest chondrogenic capacity and is best suited for future clinical trials. Method optimisation protocol: Synovial biopsies (2 or 5mm) were obtained from patients undergoing surgery. The biopsies were digested in either collagenase type I, IA, IV or II at a concentration of 0.5 or 1.0 mg/mL. Digestion was conducted at 37°C for 30, 60, 90 or 120min. To assay for the number of MPCs obtained, the cell suspension was stained with CD90 (a synovial MPC marker) and magnetically purified. The purified cells were then assayed by flow cytometry (Co-stained with a live/dead cell marker, BV510) or bright-field microscopy. Study protocol: Synovial tissues were digested in type IV collagenase for two hours to obtain a single cell suspension. The cells were subsequently stained with mesenchymal stem cell markers, including CD 90, CD 271, CD 44, CD73, and CD105, a macrophage marker, CD68. The macrophages were excluded and the remaining cells were index sorted into 96-well plates. The cells were expanded, and underwent 21-day chondrogenic, adipogenic, and osteogenic differentiation. Differentiation was assayed using RT-qPCR and histological methods. Additionally, the cells were re-analysed for marker expression after culturing. Optimisation: Synovial biopsies of 5mm produced a greater number of live CD90+ cells than 2mm biopsies. It was observed that type IV collagenase at 1mg/ML treatment for 120 min (hip) and 90 min (knee) obtained the greatest number of CD90+ MPCs from the synovium. Results: A single cell was isolated from an OA hip biopsy and was positive for the markers CD90, CD44, CD73, and negative for the markers CD68, CD271, CD105. Following differentiation, PCR analysis suggested that the cell line was able to differentiate into chondrocytes and adipocytes, but not osteoblasts. Histology data agreed with the PCR data with the adipocytes and chondrocytes having positive staining, whereas the osteoblasts were negative. FACS analysis following proliferation showed that the expression in vivo versus in vitro was the same except CD105 that became positive after proliferation in vitro. MPCs express cell surface markers that provide information as to populations have the best cartilage regeneration abilities. By determining the properties of the MPCs in OA hips that allow for better chondrogenic differentiation abilities in vitro, selecting the optimal cells for regenerating cartilage can be done more efficiently for novel cell therapies for OA

Alignment of total joint replacement in the valgus knee can be done readily with intramedullary alignment and hand-held instruments. Intramedullary alignment instruments usually are used for the femoral resection. The distal femoral surfaces are resected at a valgus angle of 5 degrees. A medialised entry point is advised because the distal femur curves toward valgus in the valgus knee, and the distal surface of the medial femoral condyle is used as reference for distal femoral resection. In the valgus knee, the anteroposterior axis is especially important as a reliable landmark for rotational alignment of the femoral surface cuts because the posterior femoral condyles are in valgus malalignment, and are unreliable for alignment. Rotational alignment of the distal femoral cutting guide is adjusted to resect the anterior and posterior surfaces perpendicular to the anteroposterior axis of the femur. In the valgus knee this almost always results in much greater resection from the medial than from the lateral condyle. Intramedullary alignment instruments are used to resect the proximal tibial surface perpendicular to its long axis. Like the femoral resection, resection of the proximal tibial surface is based on the height of the intact medial bone surface. After correction of the deformity, ligament adjustment is almost always necessary in the valgus knee. Stability is assessed first in flexion by holding the knee at 90 degrees and maximally internally rotating the extremity to stress the medial side of the knee, then maximally externally rotating the extremity to evaluate the lateral side of the knee. Medial opening greater than 4mm, and lateral opening greater than 5mm, is considered abnormally lax, and a very tight lateral side that does not open at all with varus stress is considered to be abnormally tight. Stability is assessed in full extension by applying varus and valgus stress to the knees. Medial opening greater than 2mm is considered to be abnormally lax, and a very tight lateral side that does not open at all with varus stress is considered to be too tight. Release of tight structures should be done in a conservative manner. In some cases, direct release from bone attachment is best (popliteus tendon); in others, release with pie-crusting technique is safe and effective. In knees that are too tight laterally in flexion, but not in extension, the LCL is released in continuity with the periosteum and synovial attachments to the bone. When this lateral tightness is associated with internal rotational contracture, the popliteus tendon attachment to the femur is also released. The iliotibial band and lateral posterior capsule should not be released in this situation because they provide lateral stability only in extension. The only structures that provide passive stability in flexion are the LCL and the popliteus tendon complex, so knees that are tight laterally in flexion and extension have popliteus tendon or LCL release (or both). Stability is tested after adjusting tibial thickness to restore ligament tightness on the lateral side of the knee. Additional releases are done only as necessary to achieve ligament balance. Any remaining lateral ligament tightness usually occurs in the extended position only, and is addressed by releasing the iliotibial band first, then the lateral posterior capsule, if needed. The iliotibial band is approached subcutaneously and released extrasynovially, leaving its proximal and distal ends attached to the synovial membrane. In knees initially too tight laterally in extension, but not in flexion, the LCL and popliteus tendon are left intact, and the iliotibial band is released. If this does not loosen the knee enough laterally, the lateral posterior capsule is released. The LCL and popliteus tendon rarely, if ever, are released in this type of knee. Finally, the tibial component thickness is adjusted to achieve proper balance between the medial and lateral sides of the knee. Anteroposterior stability and femoral rollback are assessed, and posterior cruciate substitution is done, if necessary, to achieve acceptable posterior stability

A prospective study was carried out to determine if recognised histological features seen at surgery could help predict those rotator cuff tendon repairs which re-ruptured. 40 rotator cuff tendon edge specimens from 40 patients’ shoulders were analysed histologically following routine mini-open rotator cuff repair. 32/40 underwent Ultrasonography, at a mean time of 35 months post-operatively, to determine repair integrity. The histological features seen at surgery were then compared to the repair integrity of the tendon from which it had been taken. Rotator cuff repairs that remained intact demonstrated a greater reparative response, in terms of increased fibrobast cellularity, cell proliferation and a thickened synovial membrane, than those repairs which reruptured. Larger tears which remained intact showed a higher degree of vasacularity and a significant inflammatory component than those that re-ruptured. Good tissue quality at the time of surgery allows the repair the best chance of remaining intact despite the size of the lesion. Routine histological analysis of the tissue biopsy, preformed in the post-operatively, can now aid the clinician in terms of early management and repair prognosis

Introduction: Pigmented villonodular synovitis is an uncommon, benign, proliferative, neoplastic process of the synovial membrane presumed to be of histiocytic origin and is likely to cause diagnostic dilemma. We present 4 cases with varied presentations in the form of increasing groin pain, inguinal mass, co-existing osteoarthritis which were subsequently confirmed to have PVNS. Methods and results: Clinical records and imaging modalities of 4 patients with histologically confirmed Pigmented villonodular synovitis of the hip, accrued from Scottish Bone Tumour Registry between 1969 and 2000 were reviewed. Discussion: PVNS of the hip is an important differential diagnosis when osteoarthritis is associated with atypical clinical picture or lytic lesions. Although it remains confined to the joint, soft tissue masses extending beyond the capsule in to retroperitoneum or anterior and posterior aspects of hip have been reported as shown here. Radiographs in early stages are normal or include a concentric joint space narrowing. MR is an important non-invasive modality for surgical planning and to define the size and extent of the lesion, recurrence, delineating between synovial proliferations and periarticular or intra-abdominal organs. The role of arthroscopy, both diagnostic and therapeutic, is rapidly emerging, although, it has its own limitations. A carefully performed total excision often prevents recurrence as can be seen in this series

In the past, the clinical outcome of earlier types of resurfacing hip arthroplasty was often characterised by a high percentage of failures and early mobilisations. An implant retrieval of a Co-Cr head and UHMWPE cup cemented resurfacing hip prosthesis was analysed. The implant was in place 11 years, without any clinical problem for nearly 10 years. The cup was highly worn. There was a complete fracture of the interface between cement and bone at the base of the femural neck. A significant hyperplastic reaction was present at the level of the synovial membrane, with fibrin deposits, hyperplasia of lining cells and a cellular infiltrate formed mostly by macrophages, with occasional giant cells and localised groups of perivascular lymphocytes. Immunohistochemical analysis showed that all lymphocytes were of the T type and that the largest part of macrophages containing debris were not activated. Inside the prosthetic head there were only traces of ossified tissue. This picture indicated that for a long time no viable bone tissue had been in contact with the cement and bone rarefaction was massive. The study shows an important cause of the failure of earlier types of hip resurfacing arthroplasty, namely the abnormal stress distribution that caused the complete bone rarefaction

The aim of this study was to observe the macroscopic and microscopic appearance of the Coracoacromial ligament and Subacromial bursa during Subacromial decompression and correlate it with the outcome at 3 months. Twenty patients with Subacromial Impingement without Rotator Cuff tear and five patients with large/massive irreparable Rotator Cuff tears who underwent a Subacromial Decompression. Patients with other shoulder pathology were excluded. Patients completed an Oxford Shoulder Score pre-operatively and their injection history was noted. At operation the shape of the acromion was noted. The macroscopic appearance of the CA ligament and the Subacromial bursa was classified as normal, mild/moderate and severe. Biopsies of the Subacromial bursa and CA ligament were taken and were analysed using histological and contempory immunocytochemical techniques. A histological analysis was performed using Mayer’s Haemotoxylin and Eosin, Toluidine Blue and Congo Red. Sections were stained with primary antibodies against PCNA (Proliferating cell nuclear antigen), Mast Cell Tryptase, CD3 (T-cell), CD20 (B cell), CD 34 (QBEnd 10), CD45 (Leucocyte Common Antigen), CD68 and D2–40 (Lymphatic Endothelial Marker). Post operatively the patients completed an Oxford Shoulder Score at 3 months. All the patients demonstrated an improvement in their Oxford Shoulder Score. The histological analysis demonstrated thickening of the synovial membrane and increased vascularity within the bursa and ligament. Increased numbers of inflammatory cells were present within the ligament and bursa of patients with impingement compared with massive rotator cuff tears. There was a relationship between outcome and the appearance of the bursa and ligament