Aims. Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism. Methods. A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry. Results. We found that PA28γ knockdown in chondrocytes can effectively improve anabolism and catabolism and inhibit inflammation, apoptosis, and ER stress. Moreover, PA28γ knockdown affected the phosphorylation of IRE1α and the expression of TRAF2, thereby affecting the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signalling pathways, and finally affecting the inflammatory response of chondrocytes. In addition, we found that PA28γ knockdown can promote the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inhibiting ER stress in chondrocytes. The use of Stattic (an inhibitor of STAT3 phosphorylation) enhanced ER stress. In vivo, we found that PA28γ knockdown effectively reduced cartilage destruction in a mouse model of OA induced by the DMM surgery. Conclusion. PA28γ knockdown in chondrocytes can inhibit anabolic and catabolic dysregulation, inflammatory response, and apoptosis in OA. Moreover, PA28γ knockdown in chondrocytes can inhibit ER stress by promoting STAT3 phosphorylation. Cite this article: Bone Joint Res 2024;13(11):659–672

Introduction. Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice. Method. OA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted. Result. OARSI scoring confirmed OA induction 4 weeks post-DMM surgery, with forced exercise exacerbating cartilage degradation regardless of intensity. No significant genotype-dependent differences were observed. Serum analysis revealed elevated cytokine levels associated with OA and inflammation in KO mice compared to WT mice 4 and 8 weeks post-surgery (VEGF-A, MCP-1, CXCL10, RANTES, MIP1-alpha, MIP1-beta, and RANKL). The observed effects were often exacerbated by intense exercise but rarely by DMM surgery. NanoCT analysis demonstrated increased sclerotic bone changes after 6 weeks of forced exercise in KO mice compared to WT mice. Conclusion. Our results suggest an OA promoting effect of exercise in early disease stages of posttraumatic OA. Intense exercise induced inflammatory processes correlated to increased cytokine levels in the serum that might exacerbate OA pathogenesis in later stages. The neuropeptide alpha-CGRP might play a role in protecting against these adverse effects

Introduction. Degenerative meniscal tears are the most common meniscal lesions, representing huge clinical and socio-economic burdens. Their role in knee osteoarthritis (OA) onset and progression is well established and demonstrated by several retrospective studies. Effective preventive measures and non-surgical treatments for degenerative meniscal lesions are still lacking, also because of the lack of specific and accurate animal models in which test them. Thus, we aim to develop and validate an accurate animal model of meniscus degeneration. Method. Three different surgical techniques to induce medial meniscus degenerative changes in ovine model were performed and compared. A total of 32 sheep (stifle joints) were subjected to either one of the following surgical procedures: a) direct arthroscopic mechanical meniscal injury; b) peripheral devascularization and denervation of medial meniscus; c) full thickness medial femoral condyle cartilage lesion. In all the 3 groups, the contralateral joint served as a control. Result. From a visual examination of the knee joint emerged a clear difference between control and operated groups, in the menisci but also in the cartilage, indicating the onset of OA-related cartilage degeneration. The meniscal and cartilaginous lesions were characterized by different severity and location in the different groups. For instance, a direct meniscal injury caused cartilaginous lesions especially in the medial part of the condyles, and the other approaches presented specific signature. Evaluation of scoring scales (e.g. ICRS score) allowed the quantification of the damage and the identification of differences among the four groups. Conclusion. We were effectively able to develop and validate a sheep model of meniscal degeneration which led to the onset of OA. This innovative model will allow to test in a pre-clinical relevant setting innovative approaches to prevent meniscal-related OA. Funding. Project PNRR-MAD-2022-12375978 funded by Italian Ministry of Health

Introduction. Osteoarthritis (OA) is a chronic degenerative disease of the entire joint leading to joint stiffness and pain (PMID:33571663). Recent evidence suggests that the sympathetic nervous system (SNS) plays a role in the pathogenesis of OA (PMID:34864169). A typical cause for long-term hyperactivity of the SNS is chronic stress. To study the contribution of increased sympathetic activity, we analyzed the progression of OA in chronically stressed mice. Method. We induced OA in male C57BL/6J mice by destabilizing the medial meniscus (DMM)(PMID:17470400) and exposed half of these mice to chronic unpredictable mild stress (CUMS)(PMID:28808696). Control groups consisted of sham-operated mice with and without CUMS exposure. After 12 weeks, CUMS efficacy was determined by assessing changes in body weight gain and activity of mice, measuring splenic norepinephrine and serum corticosterone levels. OA progression was studied by histological analysis of cartilage degeneration and synovitis, and by μCT to evaluate changes in calcified cartilage and subchondral bone microarchitecture. A dynamic weight-bearing system was used to assess OA-related pain. Result. CUMS resulted in significantly decreased body weight gain and activity, as well as increased splenic norepinephrine and serum corticosterone concentrations compared to the respective controls. Surprisingly, already DMM alone resulted in elevated stress hormone levels. CUMS significantly exacerbated cartilage degeneration and synovial inflammation and increased OA pain in DMM mice. The underlying cellular and molecular mechanisms are currently being analyzed using FACS, single cell RNAseq, and spatial proteomics. Conclusion. Overall, chronic stress exacerbates OA severity and pain. Moreover, increased levels of stress hormones were observed in OA mice without CUMS induction, suggesting a complex bi-directional interaction between the SNS and OA. Targeting the autonomic nervous system, such as attenuating the SNS but also stimulating the activity of the parasympathetic nervous system, as a counterpart of the SNS, may therefore be promising for novel preventive or causal treatments of OA

Introduction. Osteoarthritis (OA) is a predominant chronic degenerative disease exerting a deep impact on quality of life and healthcare systems. Recent evidences suggest that pyroptosis, a programmed cell death characterized by inflammatory cytokine release, may play a significant role in modulating OA pain. The aim of the study is to investigate the potential role of extracellular vesicles derived from umbilical cord Wharton's jelly (WJ-MSC EVs) in the attenuation of the pyroptotic process on human chondrocytes (hOAC) pre-treated with synovial fluid in a 3D in vitro model. Method. EVs isolated by tangential filtration of the conditioned medium of WJ-MSCs were characterized for: morphology by TEM, surface markers by WB and size by NTA. Confocal microscopy was used to identify PKH26-labelled EVs and monitor their incorporation into hOACs. The hOACs from surgical waste material of patients undergoing knee replacement, expanded, encapsulated in alginate beads were pre-treated with synovial fluid for 24 h (SF) and subsequently co-incubated with WJ-MSC EVs. We examined viability (CCK-8), metabolic activity (MTT), nitrite production (Griess) activation of the pyroptotis (IF), DNA quantification (PicoGreen) and gene expression levels of extracellular matrix (ECM) components (qPCR). One-way ANOVA analysis was used to compare the groups under exam and data were expressed as mean ± S.D. Result. WJ-MSC EVs increased hOACs viability and metabolic activity. The production of nitrites is significantly decreased compared sample group treated with SF. WJ-MSC EVs inhibited inflammasomes NLRP3 (nucleotide-binding domain, leucine-rich repeat pyrin domain containing 3) activation. The ECM catabolic genes decreased compared to the inflamed SF group for ADAMTS-5 and MMP-1. Conclusion. Our results supported the potential use of WJ-MSC EVs as a cell-free strategy for OA, overcoming the side effects of cell-therapy. Moreover, WJ-MSC EVs are able to mitigate SF-treated hOACs pyroptotic death, attenuate ECM degradation and oxidative stress counteracting the inflamed status in OA development and progression

Aims

Distal femoral osteotomies (DFOs) are commonly used for the correction of valgus deformities and lateral compartment osteoarthritis. However, the impact of a DFO on subsequent total knee arthroplasty (TKA) function remains a subject of debate. Therefore, the purpose of this study was to determine the effect of a unilateral DFO on subsequent TKA function in patients with bilateral TKAs, using the contralateral knee as a self-matched control group.

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The aim of this study was to compare patient-reported outcomes (PROMs) following isolated anterior cruciate ligament reconstruction (ACLR), with those following ACLR and concomitant meniscal resection or repair.

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In patients with a failed radial head arthroplasty (RHA), simple removal of the implant is an option. However, there is little information in the literature about the outcome of this procedure. The aim of this study was to review the mid-term clinical and radiological results, and the rate of complications and removal of the implant, in patients whose initial RHA was undertaken acutely for trauma involving the elbow.

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The primary aim of this study is to quantify and compare outcomes following a dorsally displaced fracture of the distal radius in elderly patients (aged ≥ 65 years) who are managed conservatively versus with surgical fixation (open reduction and internal fixation). Secondary aims are to assess and compare upper limb-specific function, health-related quality of life, wrist pain, complications, grip strength, range of motion, radiological parameters, healthcare resource use, and cost-effectiveness between the groups.

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The prevalence of osteoarthritis (OA) associated with instability of the shoulder ranges between 4% and 60%. Articular cartilage is, however, routinely assessed in these patients using radiographs or scans (2D or 3D), with little opportunity to record early signs of cartilage damage. The aim of this study was to assess the prevalence and localization of chondral lesions and synovial damage in patients undergoing arthroscopic surgery for instablility of the shoulder, in order to classify them and to identify risk factors for the development of glenohumeral OA.

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Closed suction subfascial drainage is widely used after instrumented posterior spinal fusion in patients with a spinal deformity. The aim of this study was to determine the effect of this wound drainage on the outcomes in patients with adolescent idiopathic scoliosis (AIS). This was a further analysis of a randomized, multicentre clinical trial reporting on patients after posterior spinal fusion using segmental pedicle screw instrumentation. In this study the incidence of deep surgical site infection (SSI) and chronic postoperative pain at two years’ follow-up are reported.

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The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms.

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Surgical approaches to cervical ossification of the posterior longitudinal ligament (OPLL) remain controversial. The purpose of the present study was to analyze and compare the long-term neurological recovery following anterior decompression with fusion (ADF) and posterior laminectomy and fusion with bone graft and internal fixation (PLF) based on > ten-year follow-up outcomes in a single centre.

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The ulna is an extremely rare location for primary bone tumours of the elbow in paediatrics. Although several reconstruction options are available, the optimal reconstruction method is still unknown due to the rarity of proximal ulna tumours. In this study, we report the outcomes of osteoarticular ulna allograft for the reconstruction of proximal ulna tumours.

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Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

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The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM).

Rotator cuff pathology is the main cause of shoulder pain and dysfunction in older adults. When a rotator cuff tear involves the subscapularis tendon, the symptoms are usually more severe and the prognosis after surgery must be guarded. Isolated subscapularis tears represent 18% of all rotator cuff tears and arthroscopic repair is a good alternative primary treatment. However, when the tendon is deemed irreparable, tendon transfers are the only option for younger or high-functioning patients. The aim of this review is to describe the indications, biomechanical principles, and outcomes which have been reported for tendon transfers, which are available for the treatment of irreparable subscapularis tears.

The best tendon to be transferred remains controversial. Pectoralis major transfer was described more than 30 years ago to treat patients with failed surgery for instability of the shoulder. It has subsequently been used extensively to manage irreparable subscapularis tendon tears in many clinical settings. Although pectoralis major reproduces the position and orientation of the subscapularis in the coronal plane, its position in the axial plane – anterior to the rib cage – is clearly different and does not allow it to function as an ideal transfer. Consistent relief of pain and moderate recovery of strength and function have been reported following the use of this transfer. In an attempt to improve on these results, latissimus dorsi tendon transfer was proposed as an alternative and the technique has evolved from an open to an arthroscopic procedure. Satisfactory relief of pain and improvements in functional shoulder scores have recently been reported following its use. Both pectoralis minor and upper trapezius transfers have also been used in these patients, but the outcomes that have been reported do not support their widespread use.

Cite this article: Bone Joint J 2024;106-B(9):970–977.

Aims. Favourable short-term outcomes have been reported following latissimus dorsi tendon transfer for patients with an irreparable subscapularis (SSC) tendon tear. The aim of this study was to investigate the long-term outcomes of this transfer in these patients. Methods. This was a retrospective study involving 30 patients with an irreparable SSC tear and those with a SSC tear combined with a reparable supraspinatus tear, who underwent a latissimus dorsi tendon transfer. Clinical scores and active range of motion (aROM), SSC-specific physical examination and the rate of return to work were assessed. Radiological assessment included recording the acromiohumeral distance (AHD), the Hamada grade of cuff tear arthropathy and the integrity of the transferred tendon. Statistical analysis compared preoperative, short-term (two years), and final follow-up at a mean of 8.7 years (7 to 10). Results. There were significant improvements in clinical scores, in the range and strength of internal rotation and aROM compared with the preoperative values in the 26 patients (87%) who were available for long-term follow-up. These improvements were maintained between short- and long-term follow-ups. Although there was a decreased mean AHD of 7.3 mm (SD 1.5) and an increased mean Hamada grade of 1.7 (SD 0.5) at final follow-up, the rate of progression of cuff tear arthropathy remained low-grade. Comparison between the isolated SSC and combined SSC and reparable supraspinatus tear groups showed no significant differences. At final follow-up, one patient (3.8%) had undergone revision surgery to a reverse shoulder arthroplasty (RSA). No neurological complications were associated with the procedure. Conclusion. Latissimus dorsi transfer for an irreparable SSC tendon tear resulted in a significant clinical improvement, particularly in pain, range and strength of internal rotation and aROM, which were maintained over a mean of 8.7 years following surgery. Given that this was a long-term outcome study, there was a low-grade progression in the rate of cuff tear arthropathy. Thus, the long-term clinical efficacy of latissimus dorsi tendon transfer in patients with irreparable SSC was confirmed as a joint-preserving procedure for these patients, suggesting it as an effective alternative to RSA in young, active patients without degenerative changes of the glenohumeral joint. Cite this article: Bone Joint J 2024;106-B(9):957–963

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.

Aims

The escalating demand for medical resources to address spinal diseases as society ages is an issue that requires careful evaluation. However, few studies have examined trends in spinal surgery, especially unscheduled hospitalizations or surgeries performed after hours, through large databases. Our study aimed to determine national trends in the number of spine surgeries in Japan. We also aimed to identify trends in after-hours surgeries and unscheduled hospitalizations and their impact on complications and costs.