Search Results (14)

Post-traumatic osteoarthritis (PTOA) is a rapidly progressing joint disorder initiated by acute injury, characterized by persistent inflammation, chondrocyte dysfunction, and extracellular matrix (ECM) degradation. Despite its clinical burden, effective disease-modifying therapies are lacking. Increasing evidence suggests that the ubiquitin–proteasome system, particularly E3 ubiquitin ligases, plays a pivotal role in regulating key pathogenic pathways involved in PTOA and represents a potentially druggable regulatory axis. In this review, we provide a comprehensive overview of the emerging roles of E3 ubiquitin ligases in PTOA, highlighting their involvement in inflammatory signaling, chondrocyte fate regulation, and cartilage matrix remodeling. We further integrate the current findings into a unified framework, in which E3 ligases act as central regulatory nodes linking injury-induced molecular responses to chronic joint degeneration. Importantly, we emphasize the pharmacological and translational potential of targeting E3 ubiquitin ligases as a novel therapeutic strategy. Recent advances in small-molecule modulators, gene-based interventions, and proteolysis-targeting chimeras (PROTACs) highlight the druggability of this regulatory system and provide new opportunities for disease-modifying treatment in PTOA. We also discuss the current challenges, including context-dependent effects, limited PTOA-specific validation, and delivery barriers. Overall, this review provides a comprehensive and therapeutically oriented perspective on E3 ubiquitin ligases in PTOA and highlights their potential as promising targets for pharmacological intervention and disease-modifying therapy. Full article

Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by chronic inflammation and progressive cartilage degradation. Mesenchymal stem cell (MSC)-based therapies have demonstrated therapeutic potential; however, increasing evidence suggests that their efficacy primarily arises from paracrine factors, highlighting the potential of cell free approaches. In this study, we developed an injectable, thermosensitive composite hydrogel incorporating adipose-derived MSC (AD-MSC) supernatant within a Pluronic F-127 (PF-127)/sodium hyaluronate (HA) matrix. The hydrogel exhibited a solution state at a low temperature and rapidly transitioned into a stable gel at a physiological temperature without chemical crosslinkers. Microstructural analysis revealed a porous, interconnected three-dimensional network favorable for the sustained release of bioactive factors. In a rat model of KOA, intra-articular administration of the AD-MSC supernatant-loaded hydrogel significantly improved joint architecture and locomotor performance, alleviated synovial inflammation, and preserved cartilage integrity. Radiographic and histological assessments demonstrated reduced cartilage degeneration and subchondral bone alterations. Moreover, the treatment markedly decreased intra-articular levels of proinflammatory cytokines (IL-1β and TNF-α) and the cartilage degradation marker CTX-II in a time-dependent manner. These findings indicated that the sustained local delivery of AD-MSC-derived supernatant effectively modulated joint inflammation and attenuated cartilage degeneration, with the hydrogel serving primarily as a delivery vehicle for these bioactive factors. This cell-free injectable biomaterial platform could offer a promising therapeutic strategy for the treatment of knee osteoarthritis. Full article

Background/Objectives: Rapidly progressive osteoarthritis of the hip (RPOH) has unique diagnostic and surgical challenges due to rapid joint degeneration and acetabular structural alterations. This study aimed to investigate correlations between preoperative spinopelvic geometry and anterior acetabular wall bone stock deficiency in RPOH patients and introduce an advanced imaging measurement techniques for cases with amputated femoral heads. Methods: A prospective observational study was conducted that enrolled 85 patients, comprising 40 with unilateral RPOH (Zazgyva Grade II or III) and 45 controls with primary osteoarthritis (OA). Preoperative spino-pelvic parameters (pelvic tilt—PT, sacral slope—SS, lumbar lordosis—LL, and T1 pelvic angle) and acetabular anterior wall characteristics (anterior center edge angle—ACEA, anterior wall index—AWI, and anterior acetabular surface area—AASA) were measured using standardized radiographic and CT imaging protocols, including a new methodology for acetabular center estimation in femoral head-amputated cases. Results: Significant differences were identified between RPOH and primary OA patients in the PT (22.5° vs. 18.9°, p = 0.032), SS (37.8° vs. 41.1°, p = 0.041), T1 pelvic angle (14.3° vs. 11.8°, p = 0.018), and anterior center edge angle (25.3° vs. 29.7°, p = 0.035). RPOH patients exhibited pronounced spinopelvic misalignment and anterior acetabular deficiencies. Conclusions: RPOH is associated with spinopelvic misalignment and anterior acetabular wall deficiency. Accurate preoperative diagnosis imaging and personalized surgical approaches specifically addressing acetabular bone stock deficiencies are mandatory in these cases. Full article

Background: Over the past few decades, shoulder arthroplasty has evolved rapidly, driven by a growing demand for surgical solutions to degenerative, traumatic, and irreparable rotator cuff-related pathologies, particularly in an aging but increasingly active population. Objective: This narrative review aims to examine the main clinical indications and the most commonly used implant designs, highlighting differences in functional outcomes, complication rates, and revision rates between anatomic total shoulder arthroplasty (ATSA) and reverse total shoulder arthroplasty (RTSA). Methods: Articles published between 2011 and 2025 were selected through PubMed and the Australian Joint Replacement Registry reports from 2023 and 2024. The included studies comprised randomized controlled trials, systematic reviews, and meta-analyses involving adult patients treated for primary osteoarthritis, proximal humerus fractures, and massive irreparable rotator cuff tears. Results: ATSA remains the preferred option in younger patients with an intact rotator cuff, due to superior outcomes in mobility and prosthesis longevity. However, glenoid component loosening remains a significant limitation. Initially reserved for irreparable cuff tears and complex fractures, RTSA has seen a progressive expansion of its indications, offering lower revision rates and satisfactory functional results, particularly in elderly patients. Recent prosthetic innovations include stemless implants, augmented glenoid components, and convertible platforms. Conclusions: The choice between ATSA and RTSA should be individualized, based on patient-specific factors such as age, rotator cuff integrity, functional demands, and bone quality. Advances in implant materials and design, together with improved patient selection, have significantly enhanced clinical outcomes. Full article

Rapidly progressive hip osteoarthritis (RPOH) is a rare and severe form of osteoarthritis (OA), marked by the rapid degeneration and destruction of the femoral head, often within months. Despite its unclear etiology, several factors such as subchondral fractures and immune responses have been proposed as possible contributors. This narrative review aims to synthesize current knowledge on the pathogenesis, risk factors, clinical presentation, imaging features, and grading systems of RPOH. Predominantly affecting elderly females, RPOH presents distinctive challenges in both diagnosis and management due to its abrupt onset and severity. Known risk factors include advanced age, female gender, obesity, intra-articular corticosteroids use, and long-term hemodialysis. Clinically, RPOH is characterized by severe pain during active weight-bearing movements, despite patients presenting a normal range of motion during passive examination in the early stages. While several classification systems exist, there is no universal standard, complicating differential diagnosis and clinical approaches. This review emphasizes the necessity for early diagnostic methods utilizing specific biomarkers, rapid differential diagnosis, and targeted, personalized interventions based on individual risk factors. Full article

Knee osteoarthritis is a chronic, progressive disease that rapidly progresses to severe stages. Reliable and accurate diagnosis, combined with the implementation of preventive lifestyle modifications before irreversible damage occurs, can effectively protect patients from becoming an inactive population. Artificial intelligence continues to play a pivotal role in computer-aided diagnosis with increasingly convincing accuracy, particularly in identifying the severity of knee osteoarthritis according to the Kellgren–Lawrence (KL) grading scale. The primary objective of this literature review is twofold. Firstly, it aims to provide a systematic analysis of the current literature on the main artificial intelligence models used recently to predict the severity of knee osteoarthritis from radiographic images. Secondly, it constitutes a critical review of the different methodologies employed and the key elements that have improved diagnostic performance. Ultimately, this study demonstrates that the considerable success of artificial intelligence systems will reinforce healthcare professionals’ confidence in the reliability of machine learning algorithms, facilitating more effective and faster treatment for patients afflicted with knee osteoarthritis. In order to achieve these objectives, a qualitative and quantitative analysis was conducted on 60 original research articles published between 1 January 2018 and 15 May 2024. Full article

Background: Rapidly progressive osteoarthritis of the hip (RPOH) is a rare syndrome that involves the femoral head and acetabulum. Methods: We analyzed the incidence of RPOH in 2022. The inclusion criteria included a clinical history of pain for 1–6 months and a decrease in joint space of > 2 mm within one year or a decrease in joint space by 50% in that time accompanied by femoral and/or acetabular bone destruction. Exclusion: There are no other destructive arthropathies and no evolutionary radiological image sequence. Results: There were 15 patients, 16 hips, an incidence around 3.17%, a 1:1 laterality ratio, and 1 bilateral affected. The mean average age is 77.35 years. The male/female ratio is 1:2. The average BMI is 31.2. The time of the onset of the symptoms to the patient’s diagnosis is 5 months. The functionally modified Harris scale (MHS) had an average score of 30 points. They had surgery hip arthroplasty with a cementless cup in all cases, a revision cup in one of them, and a double mobility cup in the other, with the stem cemented three times. There were no post-surgical complications. Functionally was achieved at 3 months. The average MHS is 70 at 12 months. The average MHS is 85. Conclusions: RPOH is an idiopathic entity characterized by great clinical involvement and rapid radiological evolution. It is most common in women around 77 years of age. The bone quality requires surgical alternatives to implants, and it has good functional recovery post-surgery. Full article

Background: Rapidly destructive osteoarthritis (RDO) of the hip joint is characterised by the rapid destruction of the femoral head with or without acetabular involvement. There has been increasing interest in this disease over the past years; however, the entity is still poorly understood, and its pathophysiology remains unknown. Yet, there is ample evidence today that increased bone metabolism might play a role in the onset and progression of the disease. Vitamin D is of utmost importance to maintain a balanced bone metabolism. However, whether vitamin D deficiency is involved in disease development remains to be elucidated. Further, the vitamin D status of patients with RDO has not yet been analysed. For this reason, the objective of this study was to assess the vitamin D status of patients with RDO. Moreover, the aim was to clarify whether there is a difference in the vitamin D status of patients with RDO compared with patients with primary osteoarthritis (OA). Methods: In this single-centre analysis, the 25(OH)D, PTH, and calcium levels of 29 patients who presented with RDO between 2020 and 2022 were assessed. Results: Altogether, 97% of patients (28/29) were vitamin D deficient, a further 3% (1/29) were vitamin D insufficient, and not a single patient presented with a sufficient vitamin D status. Notably, the vitamin D levels of RDO patients (mean = 11.04 ng/mL) were significantly lower than the vitamin D levels of patients with OA (mean = 22.16 ng/mL, p = 0.001). Conclusion: In conclusion, we found a widespread and high rate of vitamin D deficiency in patients with RDO. Hence, we believe that 25(OH)D status should routinely be analysed in these patients. Full article

Osteoarthritis (OA) is a condition that can cause substantial pain, loss of joint function, and a decline in quality of life in patients. Numerous risk factors, including aging, genetics, and injury, have a role in the onset of OA, characterized by structural changes within the joints. Most therapeutic approaches focus on the symptoms and try to change or improve the structure of the joint tissues. Even so, no treatments have been able to stop or slow the progression of OA or give effective and long-lasting relief of symptoms. In the absence of disease-modifying drugs, regenerative medicine is being investigated as a possible treatment that can change the course of OA by changing the structure of damaged articular cartilage. In regenerative therapy for OA, mesenchymal stem cells (MSCs) have been the mainstay of translational investigations and clinical applications. In recent years, MSCs have been discovered to be an appropriate cell source for treating OA due to their ability to expand rapidly in culture, their nontumorigenic nature, and their ease of collection. MSCs’ anti-inflammatory and immunomodulatory capabilities may provide a more favorable local environment for the regeneration of injured articular cartilage, which was thought to be one of the reasons why they were seen as more suited for OA. In addition to bone marrow, MSCs have also been isolated from adipose tissue, synovium, umbilical cord, cord blood, dental pulp, placenta, periosteum, and skeletal muscle. Adipose tissue and bone marrow are two of the most essential tissues for therapeutic MSCs. Positive preclinical and clinical trial results have shown that, despite current limitations and risks, MSC-based therapy is becoming a promising approach to regenerative medicine in treating OA. Full article

With the insufficient satisfaction rates and high cost of operative treatment for osteoarthritis (OA), alternatives have been sought. Furthermore, the inability of current medications to arrest disease progression has led to rapidly growing clinical research relating to mesenchymal stem cells (MSCs). The availability and function of MSCs vary according to tissue source. The three primary sources include the placenta, bone marrow, and adipose tissue, all of which offer excellent safety profiles. The primary mechanisms of action are trophic and immunomodulatory effects, which prevent the further degradation of joints. However, the function and degree to which benefits are observed vary significantly based on the exosomes secreted by MSCs. Paracrine and autocrine mechanisms prevent cell apoptosis and tissue fibrosis, initiate angiogenesis, and stimulate mitosis via growth factors. MSCs have even been shown to exhibit antimicrobial effects. Clinical results incorporating clinical scores and objective radiological imaging have been promising, but a lack of standardization in isolating MSCs prevents their incorporation in current guidelines. Full article

The challenge of osteoarthritis (OA) is to find a minimally invasive orthobiological therapy to contrast OA progression, on inflammatory and structural fronts. The aim of the present study is to compare the effects of an intra-articular injection of three orthobiological treatments, autologous culture expanded adipose-derived mesenchymal stromal cells (ADSCs), autologous stromal vascular fraction (SVF) and allogenic culture expanded amniotic epithelial stem cells (AECs), in an animal model of OA. OA was induced in 24 sheep by bilateral lateral meniscectomy and, at 3 and 6 months post-treatment, the results were analyzed with macroscopy, histology, histomorphometry, and biochemistry. All the three treatments showed better results than control (injection of NaCl), but SVF and AECs showed superiority over ADSCs, because they induced higher cartilage regeneration and lower inflammation. SVF showed better results than AECs at 3 and 6 months. To conclude, SVF seems to be more favorable than the other biological options, because it is easily obtained and rapidly used after harvesting, with good healing potential. AECs cause no discomfort and could be also considered for the treatment of OA joints. Full article

Osteoarthritis (OA) is a common degenerative joint disease treated mostly symptomatically before approaching its definitive treatment, joint arthroplasty. The rapidly growing prevalence of OA highlights the urgent need for a more efficient treatment strategy and boosts research into the mechanisms of OA incidence and progression. As a multifactorial disease, many aspects have been investigated as contributors to OA onset and progression. Differences in gender appear to play a role in the natural history of the disease, since female sex is known to increase the susceptibility to its development. The aim of the present review is to investigate the cues associated with gender by analyzing various hormonal, anatomical, molecular, and biomechanical parameters, as well as their differences between sexes. Our findings reveal the possible implications of gender in OA onset and progression and provide evidence for gaps in the current state of art, thus suggesting future research directions. Full article

Articular cartilage, as a hydrated soft tissue which covers diarthrodial joints, has a pivotal role in the musculoskeletal system. Osteoarthritis is the most common degenerative disease that affects most individuals over the age of 55. This disease affects the elasticity, lubrication mechanism, damping function, and energy absorption capability of articular cartilage. In order to investigate the effect of osteoarthritis on the performance of articular cartilage, the mechanical behavior of human knee articular cartilage was experimentally investigated. Progressive cyclic deformation was applied beyond the physiological range to facilitate degradation of the tissue. The relaxation response of the damaged tissue was modeled by means of a fractional-order nonlinear viscoelastic model in the framework of finite deformations. It is shown that the proposed fractional model well reproduces the tissue’s mechanical behavior using a low number of parameters. Alteration of the model parameters was also investigated throughout the progression of tissue damage. This helps predict the mechanical behavior of the osteoarthritic tissue based on the level of previous damage. It is concluded that, with progression of osteoarthritis, the articular cartilage loses its viscoelastic properties such as damping and energy absorption capacity. This is also accompanied by a loss of stiffness which deteriorates more rapidly than viscosity does throughout the evolution of tissue damage. These results are thought to be significant in better understanding the degradation of articular cartilage and the progression of OA, as well as in the design of artificial articular cartilages. Full article

Exosomes are nanosized vesicles (30–140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration. Full article