Sore knees — why does cartilage wear down?

Aim of the study: During anterior cruciate ligament (ACL) injury, the large external forces responsible for ligament rupture cause a violent impact between tibial and femoral articular cartilage, which is transferred to bone resulting in bone bruise detectable at MRI. Several aspects remain controversial and await evidence on how this MRI finding should be managed while addressing the ligament lesion.

Results: The search identified 415 records and, after an initial screening according to the inclusion/exclusion criteria, 83 papers were used for analysis, involving a total of 10,047 patients. Bone bruise has a high prevalence (78% in the most recent papers), with distinct patterns related to the mechanism of injury. This MRI finding is detectable only in a minority of cases the first few months after trauma, but its presence and persistence have been correlated to a more severe joint damage that may affect the degenerative progression of the entire joint, with recent evidence suggesting possible effects on long-term clinical outcome. This systematic review of the literature documented a growing interest on bone bruise associated with ACL injury, highlighting aspects which could provide to orthopaedic surgeons evidence-based suggestions in terms of clinical relevance when dealing with patients affected by bone bruise following ACL injury.

Aim of the study: The damping system ensured by the osteochondral (OC) unit is essential to deploy the forces generated within load-bearing joints during locomotion, allowing furthermore low-friction sliding motion between bone segments. The OC unit is a multi-layer structure including articular cartilage, as well as subchondral and trabecular bone.

Results: Most advanced studies have tested and modelled multiple tissues of the same OC unit but have done so individually rather than through integrated approaches. Therefore, efforts should be made in simultaneously evaluating the comprehensive response of the OC unit to intra-articular loads and the interplay between the OC tissues. In this regard, a multidisciplinary approach combining complementary techniques, e.g., full-field imaging, mechanical testing, and computational approaches, should be implemented and validated. Furthermore, the next challenge entails transferring this assessment to a non-invasive approach, allowing its application in vivo, in order to increase its diagnostic and prognostic potential.

Aim of the study: Chondromalacia patellae (CMP), also known as runner's knee, typically occurs in young patients, which is characterized by anterior knee pain (AKP) that is associated with visible changes in patellar cartilage. The initial pathological changes include cartilage softening, swelling, and edema.

Results: Various efforts including cell therapy and tissue emerge for cartilage regeneration exhibit as the promising regime, especially in the application of mesenchymal stem cells (MSCs). Intra-articular injections of variously sourced MSC are found safe and beneficial for treating CMP with improved clinical parameters, less invasiveness, symptomatic relief, and reduced inflammation. The mechanism of MSC injection remains further clinical investigation and is tremendously promising for CMP treatment. In this short review, etiology, MRI diagnosis, and treatment in CMP, especially the treatment of the cell-based therapies, are reviewed.

Aim of the study: Knee osteoarthritis is a chronic degenerative disease companied with chronic knee pain and dysfunction. However, the etiology and pathogenesis of knee osteoarthritis were unclear.

Results: The major pathological hallmarks of knee osteoarthritis included subchondral bone sclerosis, articular cartilage degeneration, arthrosynovitis, and osteophyte. With the acceleration of the aging process in China, the treatment of knee arthritis and the methods to improve the quality of life have become the focus of medical staff. Currently, therapies in clinical practice include surgery and nonoperative treatment; however, the clinical effects of different individuals at different stages will still be very different. This article reviews the recent advances in the treatment of knee osteoarthritis from three aspects: nonsurgical treatment, surgical treatment, and modern new medical means.

Aim of the study: Osteoarthritis (OA) is an aging-related degenerative joint disease with a poorly defined mechanism. Here we report that kindlin-2 is highly expressed in articular chondrocytes and downregulated in the degenerated cartilage of aged mice and patients with OA.

Results: Pharmacological inhibition of Stat3 activation or genetic ablation of Stat3 in chondrocytes reverses aberrant accumulation of Runx2 and extracellular-matrix-degrading enzymes and limits OA deteriorations caused by kindlin-2 deficiency. Deleting Runx2 in chondrocytes reverses structural changes and OA lesions caused by kindlin-2 deletion without downregulating p-Stat3. Intra-articular injection of AAV5-kindlin-2 decelerates progression of aging- and instability-induced knee joint OA in mice. Collectively, we identify a pathway consisting of kindlin-2, Stat3 and Runx2 in articular chondrocytes that is responsible for maintaining articular cartilage integrity and define a potential therapeutic target for OA.

Aim of the study: Recent studies have shed light on the cellular and molecular mechanisms that link subchondral bone remodelling and angiogenesis in knee osteoarthritis (OA). Type H vessels are a newly identified bone blood vessel characterized by high expression of CD31 and endomucin that are coupled with osteogenesis.

Results: Factors including mechanical loading, TGF-β1, platelet-derived growth factor type BB, the osteoprotegerin-RANK ligand-RANK system, osteopontin, mechanistic target of rapamycin, VEGF, stromal cell-derived factor l and prostaglandin E2 participate in the formation of type H vessels in osteoarthritic subchondral bone. In this review, we summarize the current understanding of type H vessels in knee OA, as well as the signalling pathways involved and potential therapeutic medicines. In future, the pathogenesis of knee OA could be further clarified by connecting type H vessels and the design of new disease-modifying osteoarthritis drugs. However, further experiments are needed to determine the upstream signals regulating type H vessel formation in osteoarthritic subchondral bone.

Aim of the study: Articular cartilage is a connective tissue lining the surfaces of synovial joints. When the cartilage severely wears down, it leads to osteoarthritis (OA), a debilitating disease that affects millions of people globally.

Results: Although recent advances in high-throughput OMICS technologies have enabled molecular-level characterization of tissues and organs at an unprecedented resolution, thorough molecular profiling of articular chondrocytes has not yet been undertaken, which may be in part due to the technical difficulties in isolating chondrocytes from dense cartilage ECM. In this study, we profiled articular cartilage from healthy and injured mouse knee joints at a single-cell resolution and identified nine chondrocyte subtypes with distinct molecular profiles and injury-induced early molecular changes in these chondrocytes. We also compared mouse chondrocyte subpopulations to human chondrocytes and evaluated the extent of molecular similarity between mice and humans. This work expands our view of chondrocyte heterogeneity and rapid molecular changes in chondrocyte populations in response to joint trauma and highlights potential mechanisms that trigger cartilage degeneration.

Aim of the study: This study aimed to establish and validate a rat model of patellofemoral osteoarthritis (PFOA) induced by patellar instability and to characterize its early degenerative features and compartment specificity.

Results: At 1 week after surgery, patellofemoral cartilage showed surface irregularity, disrupted zonal architecture, and abnormal chondrocyte arrangement, with progressive worsening over time. In contrast, tibiofemoral changes were milder and appeared later. Safranin O-Fast Green and toluidine blue staining showed earlier and more pronounced loss of proteoglycans and glycosaminoglycans in patellofemoral cartilage than in tibiofemoral cartilage, accompanied by an earlier reduction in positively stained area. Compared with controls, PIICP levels in synovial lavage fluid and serum decreased at all postoperative time points, whereas MMP-13, CTX-II, and COMP levels increased (P < 0.05). These changes were more pronounced at 2 and 3 weeks than at 1 week, with no significant difference between 2 and 3 weeks, suggesting that the model reached a relatively stable early degenerative phase by approximately 2 weeks after surgery.