Aims. This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Methods. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610

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The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI).

Osteoarthritis (OA) is an inflammatory disease affecting the complete synovial joint including the cartilage layer and the subchondral bone plate. Due to the multifactorial causes and the not yet completely resolved molecular mechanisms, it lacks a gold standard treatment to mitigate OA. Hence, biomaterials capable of delaying or preventing OA are a promising alternative or supplement to antiphlogistic and surgical interventions. Magnesium (Mg) and its alloys are among the promising biomaterials with osteoinductive effects. This work investigated the impact of Mg micro cylinders (length ≈of 1.0 mm and width of 0.5 mm) in vitro, in favoring joint regeneration together with preventing OA progression. Therefore, a mesenchymal stem cell line (SCP-1) was applied in order to assess the compatibility of the degradable material. Furthermore, an in vitro OA model utilizing SCP-1 cells based on the supplementation of the cytokines; IL-1β, TNF-α was established and disclosed the capability of Mg microparticles in differentiating SCP-1 cells into chondrogenic and osteogenic lineages proven through extracellular matrix staining and gene marker analysis. A concentration above 10 mM revealed a reduction in the cell viability by 50 %. An increase in the expression of collagens especially and proteoglycans (COL2A1, Aggrecan) as extracellular matrix proteins as well as an increase in osteogenic marker (ALP, BMP2) favoring the mineralization process were observed. The inflammatory condition reduced the viability and productivity of the applied stem cell line. However, the application of Mg microparticles induced a cell recovery and reduction of inflammation marker such as MMP1 and IL6. The cytocompatible and the ability of Mg microparticles in supporting bone and cartilage repair mechanisms in vitro even under inflammatory conditions make biodegradable Mg microparticles a suitable implant material to treat OA therapy. Acknowledgements: This project OAMag was funded by the German Research Foundation (project number 404534760). The author thank Dr. Björn Wiese (hereon) for the production of Mg based material and Prof. Böcker (MUM Musculoskeletal University Center Munich) for the provision of SCP-1 cell line

Aims. Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods. We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results. EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of β1 and β3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate β1 and β3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1β-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/β) and phospholipase C gamma 1 (PLC-γ1). Conclusion. EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA. Cite this article: Bone Joint Res 2023;12(12):734–746

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Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

Cite this article: Bone Joint Res 2023;12(10):654–656.

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Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

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.

There is no optimal therapy to stop or cure chondral degeneration in osteoarthritis (OA). Beside cartilage, subchondral bone is involved. The often sclerotic bone is mechanically less solid which in turn influences negatively chondral quality. Microfracturing as therapeutic technique aims to enhance bone quality but is applied only in smaller cartilage lesions. The osteoproliferative properties of Magnesium (Mg) have been shown repeatedly^1-3. The present study examined the influence of micro-scaled Mg cylinders compared to sole drilling in an OA model.

Ten New Zealand White rabbits underwent anterior crucial ligament transection. During 12 weeks after surgery, the animals developed OA as previously described⁴. In a second surgery, half of the animals received 20 drill holes (ø 0.5mm) and the other half received 20 drill holes, which were additionally filled with one Mg cylinder each. Extracapsular plication was performed in all animals. During the follow-up of 8 weeks three µ-computed tomographic (µCT) scans were performed: immediately after surgery and after four and eight weeks. Changes of bone volume, trabecular thickness and bone density were calculated and compared.

µCT evaluation showed an increase in bone volume and trabecular thickness in both groups. This increase was significantly higher in rabbits which received Mg cylinders showing thrice as high values for both parameters (bone volume: Mg group +44.5%, drilling group +15.1%, p≤0.025; trabecular thickness: Mg group +53.2%, drilling group +16.9%, p≤0.025). Also bone density increased in both groups, but on a distinctly lower level and with no significant difference.

Although profound higher bone volume was found after implantation of Mg cylinders, µCT showed similar levels of bone density indicating adequate bone quality in this OA model. Macroscopic and histological evaluation of cartilage condition have to reveal possible impact on OA progression. Additionally, current examination implement different alloys and influence on lameness.

Many factors have been reported to affect the functional survival of OCA transplants, including chondrocyte viability at time of transplantation, rate and extent of allograft bone integration, transplantation techniques, and postoperative rehabilitation protocols and adherence. The objective of this study was to determine the optimal subchondral bone drilling technique by evaluating the effects of hole diameter on the material properties of OCAs while also considering total surface area for potential biologic benefits for cell and vascular ingrowth. Using allograft tissues that would be otherwise discarded in combination with deidentified diagnostic imaging (MRI and CT), a model of a large shell osteochondral allograft was recreated using LS-PrePost and FEBio based on clinically relevant elastic material properties for cortical bone, trabecular bone, cartilage, and hole ingrowth tissue. The 0.8 mesh size model consisted of 4 mm trabecular bone, 4 mm cortical bone, and 3 mm cartilage sections that summed to a cross-sectional area of 1600 mm2 (40 mm x 40 mm). Holes were modeled to be 4mm deep in relation to clinical practice where holes are drilled from the deep margin of subchondral trabecular bone to the cortical subchondral bone plate. To test the biomechanic variations between drill hole sizes, models with hole sizes pertinent to standard-of-care commercially available orthopaedic drill sizes of 1.1mm, 2.4 mm, or 4.0 mm holes were loaded across the top surface over a one second duration and evaluated for effective stress, effective strain, 1st principal strain, and 3rd principal strain in compressive conditions. Results measured effective stress and strain and 1st and 3rd principal strain increased with hole depth. The results of the present FEA modeling study indicate that the larger 4.0 mm diameter holes were associated with greater stresses and strains within OCA shell graft, which may render the allograft at higher risk for mechanical failure. Based on these initial results, the smaller diameter 2.4 mm and 1.1 mm holes will be further investigated to determine optimal number, configuration, and depth of subchondral drilling for OCA preparation for transplantation

Despite the growing success of OCA transplantation in treating large articular cartilage lesions in multiple joints, revisions and failures still occur. While preimplantation subchondral drilling is intended to directly decrease allograft bioburden and has been associated with significant improvements in outcomes after OCA transplantation, the effects of size, number, and spacing of subchondral bone drill sites have not been fully evaluated. This study aimed to investigate the effects of drill size with or without pulse-lavage of OCA subchondral bone by quantifying remnant marrow elements using histomorphometry. With IRB and ACUC approvals, human and canine OCAs were acquired for research purposes. Portions of human tibial plateau OCAs acquired from AATB-certified tissue banks that would otherwise be discarded were recovered and sectioned into lateral and medial hemiplateaus (n=2 each) with a thickness of 7 mm. Canine femoral condyles and tibial plateaus were split into lateral and medial components with a thickness of 7 mm (n=8). Using our clinical preimplantation preparation protocol, holes were drilled into the subchondral bone of each condyle and hemiplateau OCA using either 1.6 mm OD or 3.2 mm OD drill bits from the cut surface to the cortical subchondral bone plate. One femoral condyle and one hemiplateau per drill bit size were pulse-lavaged while the corresponding OCAs were not. The mean total %-fill remaining marrow elements for each treatment group was calculated. Little to no quantifiable bone marrow element retention was noted to remain within the subchondral bone of human or canine OCA specimens after subchondral drilling of allograft bone with either drill bit size evaluated and with or without pulse-lavage. The %-fill was consistent across zones, ranging from 1-5%. This project was designed to provide a preliminary histologic evaluation of the effects of drill size on OCA preimplantation preparation efficacy based on amount of remaining bone marrow elements in human and canine femoral condyle and tibial plateau specimens. Based on these initial findings, choice of drill bit size for OCA subchondral drilling may need to be based on the associated biomechanical effects rather than effects on donor bone marrow element removal

Aims

Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2^-/-) display accelerated bone growth.

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In this study, we aimed to explore surgical variations in the Femoral Neck System (FNS) used for stable fixation of Pauwels type III femoral neck fractures.

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Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model.

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The main aims were to identify risk factors predictive of a radiolucent line (RLL) around the acetabular component with an interface bioactive bone cement (IBBC) technique in the first year after THA, and evaluate whether these risk factors influence the development of RLLs at five and ten years after THA.

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The present study investigates the effectiveness of platelet-rich plasma (PRP) gel without adjunct to induce cartilage regeneration in large osteochondral defects in a rabbit model.

Joint surface restoration of deep osteochondral defects represents a significant unmet clinical need. Moreover, untreated lesions lead to a high rate of osteoarthritis. The current strategies to repair deep osteochondral defects such as osteochondral grafting or sandwich strategies combining bone autografts with ACI/MACI fail to generate long-lasting osteochondral interfaces. Herein, we investigated the capacity of juvenile Osteochondral Grafts (OCGs) to repair osteochondral defects in skeletally mature animals. With this regenerative model in view, we set up a new biological, bilayered, and scaffold-free Tissue Engineered (TE) construct for the repair of the osteochondral unit of the knee. Skeletally immature (5 weeks old) and mature (11 weeks old) Lewis rats were used. Cylindrical OCGs were excised from the intercondylar groove of the knee of skeletally immature rats and transplanted into osteochondral defects created in skeletally mature rats. To create bilayered TE constructs, micromasses of human periosteum-derived progenitor cells (hPDCs) and human articular chondrocytes (hACs) were produced in vitro using chemically defined medium formulations. These constructs were subsequently implanted orthotopically in vivo in nude rats. At 4 and 16 weeks after surgery, the knees were collected and processed for subsequent 3D imaging analysis and histological evaluation. Micro-computed tomography (µCT), H&E and Safranin O staining were used to evaluate the degree of tissue repair. Our results showed that the osteochondral unit of the knee in 5 weeks old rats exhibit an immature phenotype, displaying active subchondral bone formation through endochondral ossification, the absence of a tidemark, and articular chondrocytes oriented parallel to the articular surface. When transplanted into skeletally mature animals, the immature OCGs resumed their maturation process, i.e., formed new subchondral bone, partially established the tidemark, and maintained their Safranin O-positive hyaline cartilage at 16 weeks after transplantation. The bilayered TE constructs (hPDCs + hACs) could partially recapitulate the cascade of events as seen with the immature OCGs, i.e., the regeneration of the subchondral bone and the formation of the typical joint surface architecture, ranging from non-mineralized hyaline cartilage in the superficial layers to a progressively mineralized matrix at the interface with a new subchondral bone plate. Cell-based TE constructs displaying a hierarchically organized structure comprising of different tissue forming units seem an attractive new strategy to treat osteochondral defects of the knee

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Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process.