Subchondral bone changes in patients with early degenerative joint disease.

WNT5A is a novel regulator of cytokine and chemokine expression in bone marrow stromal cells

To evaluate the effects of low frequency whole-body vibration (WBV) on degeneration of articular cartilage and subchondral bone in mice with destabilization of the medial meniscus (DMM)induced osteoarthritis(OA) and mice with normal knee. Ten-week-old C57BL/6J male mice received DMM on right knees, while the left knees performed sham operation. There were six groups: DMM, SHAM DMM, DMM+WBV,SHAM DMM+WBV, DMM+ NON-WBV and SHAM DMM+NON-WBV. After four weeks, the knees were harvested from the DMM and SHAM DMM group. The remaining groups were treated with WBV (10 Hz) or NON-WBV. Four weeks later, the knees were harvested. Genes, containing Aggrecan(Acan) and CollagenⅡ(Col2a1), Matrix Metalloproteinases 3 and 13(MMP3,13), TNFα and IL6, were measured and staining was also performed. OA was graded with OARSI scores, and tibial plateaubone volume to tissue volume ratio(BV/TV), bone surface area to bone volume ratio (BS/BV), trabecular number(Tb.N) and trabecular thickness separation(TS) between groups were analyzed. Increased OARSI scores and cartilage degradation were observed after WBV. BV/TV, Tb.N and TS were not significant between the groups. Significant reductions were observed in MMP3, MMP13, Col2a1, Acan, TNFα and IL6 in the DMM+WBV compared to SHAM DMM+WBV group. BV/TV, BS/BV, Tb.N, TS and OARSI scores were not significantly changed in the left knees. IL6 expression in the SHAM DMM+WBV group was significantly increased compared with the SHAM DMM+ NON-WBV group, while Col2a1, Acan and MMP13 expression decreased. WBV accelerated cartilage degeneration and caused slight changes in subchondral bone in a DMM-induced OA model. WBV had no morphologic effect on normal joints.

Subchondral bone osteoblasts can induce chondrocyte mineralization during osteoarthritis and this process is relevant to cartilage degradation

Osteoarthritis (OA) is characterized not only by cartilage degeneration, but also subchondral bone changes. The subchondral bone plate (SBP) plays an important role in cartilage metabolism, and elucidation of the relationship between the SBP and cartilage degeneration would be helpful to determine the most appropriate treatment strategy for ankle OA. The purpose of this study was to evaluate the SBP and to compare it with cartilage degeneration with arthroscopic findings. Computed tomography (CT) was used to compare the thickness of the SBP of 11 ankle OA patients with that of 11 non-ankle OA patients in 9 areas of the talar dome. The French Society of Arthroscopy (SFA) grading system was used to analyze the relationship between findings on the thickness of SBP and on articular cartilage degeneration in ankle OA. The SBP in ankle OA was significantly thicker than that of the non-OA ankle. The more severe the articular cartilage degeneration, the thicker the SBP became. The SBP on the sclerotic trabecular bone was significantly thicker than that on decreased trabecular bone. The SFA grade for sclerotic subchondral bone was significantly higher than that for decreased trabecular bone. This study shows that the thickness of SBP and the findings of subchondral bone such as decreased trabecular bone and sclerosis in CT are related to the cartilage degeneration of ankle OA, although a small number of patients were analyzed. Level III, comparative series.

To establish a histopathological scoring system for changes in subchondral bone in murine models of knee osteoarthritis (OA), three key parameters, subchondral bone plate (Subcho.BP) consisting of the combination of Subcho.BP.thickness (Subcho.BP.Th) and angiogenesis, bone volume (BV/TV) and osteophytes, were selected. The new grading system was tested in two mouse OA models, (1) senescence accelerated mouse (SAM)-prone 8 (SAMP8) as spontaneous OA model with SAM-resistant 1 (SAMR1) as control; (2) destabilization of the medial meniscus in C57BL/6 mice as surgical OA model. Results of the spontaneous OA model showed that Subcho.BP.Th was significantly wider, angiogenesis was greater, and BV/TV was higher in SAMP8 than SAMR1. Notably, subchondral bone score was dramatically higher in SAMP8 at 6 weeks than SAMR1, while OARSI cartilage scores became higher only at 14 weeks. In the surgical OA model, the results were similar to the spontaneous OA model, but osteophytes appeared earlier. There were strong correlations both in Subcho.BP.Th and BV/TV between this scoring system and µCT (r = 0.89, 0.84, respectively). Inter-rater reliabilities for each parameter using this system were more than 0.943. We conclude that this new histopathological scoring system is readily applicable for evaluating the early changes in aging and OA-affected murine subchondral bone.

Osteoarthritis is a disease of synovial joints that involves articular cartilage breakdown with accompanying bone changes, including subchondral sclerosis and osteophytosis. However, conflicting data have been reported concerning the cause-and-effect relationship, if any, between these changes. The authors studied the subchondral plate (subchondral bone plus calcified cartilage) in relation to the degree of articular cartilage degeneration on the distal articular surface of the first metatarsal, a region prone to osteoarthritis. No correlation was found between subchondral plate thickness or porosity and the degree of cartilage degeneration in the study sample of 96 metatarsals. Owing to the suggestion that initiation of cartilage fibrillation may be a result of steep stiffness gradients in the subchondral bone, the ratios of subchondral plate thickness in adjacent regions of the metatarsal head were examined in detail, but no correlation was found with subchondral degeneration. Thus increases in subchondral bone thickness are not associated with increases in cartilage degeneration on the first metatarsal, which may imply that subchondral bone changes do not cause osteoarthritis in this joint.

Osteoarthritis is traditionally associated with cartilage degeneration although is now widely accepted as a whole-joint disease affecting the entire osteochondral unit; however site-specific cartilage and bone material properties during healthy ageing and disease are absent limiting our understanding. Cadaveric specimens (n = 12; 31–88 years) with grades 0–4 osteoarthritis, were dissected and spatially correlated cartilage, subchondral and trabecular bone samples (n = 8 per cadaver) were harvested from femoral and tibial localities. Nanoindentation was utilised to obtain cartilage shear modulus (G′) and bone elastic modulus (E). Cartilage G′ is strongly correlated to age (p = 0.003) and osteoarthritis grade (p = 0.007). Subchondral bone E is moderately correlated to age (p = 0.072) and strongly correlated to osteoarthritis grade (p = 0.013). Trabecular bone E showed no correlation to age (p = 0.372) or osteoarthritis grade (p = 0.778). Changes to cartilage G′ was significantly correlated to changes in subchondral bone E (p = 0.007). Results showed preferential medial osteoarthritis development and moderate correlations between cartilage G′ and sample location (p = 0.083). Also demonstrated for the first time was significant correlations between site-matched cartilage and subchondral bone material property changes during progressive ageing and osteoarthritis, supporting the role of bone in disease initiation and progression. This clinically relevant data indicates a causative link with osteoarthritis and medial habitual loading.

Osteopontin (OPN) has been proved to be closely related to the pathogenesis of osteoarthritis (OA), but the role of OPN in the pathogenesis of OA has not been fully clarified. Current studies on OPN in OA mostly focus on articular cartilage, synovial membrane and articular fluid, while ignoring its role in OA subchondral bone turnover and remodeling. In this study, we used a destabilization OA mouse model to investigate the role of OPN in OA subchondral bone changes. Our results indicate that increased expression of OPN accelerates the turnover and remodeling of OA subchondral bone, promotes the formation of h-type vessels in subchondral bone, and mediates articular cartilage degeneration induced by subchondral bone metabolism. In addition, our results confirmed that inhibition of PI3K/AKT signaling pathway inhibits OPN-mediated OA subchondral bone remodeling and cartilage degeneration. This study revealed the role and mechanism of OPN in OA subchondral bone, which is of great significance for exploring specific biological indicators for early diagnosis of OA and monitoring disease progression, as well as for developing drugs to regulate the metabolism and turnover of subchondral bone and alleviate the subchondral bone sclerosis of OA.

Deteriorating subchondral bone microstructure accelerates osteoarthritis progression in developmental dysplasia of the hip than in primary osteoarthritis

Osteoarthritis (OA) is a degenerative joint disorder in which progressive articular cartilage loss occurs alongside pathological changes in subchondral bone and other joint tissues. The pathophysiological role of bone in OA has been a point of interest for many years and has resurfaced again in recent years as a potential target for new treatments. Articular cartilage and subchondral bone together form the osteochondral unit. Its homeostasis and integrity are reliant on biochemical crosstalk and biomechanical interplay between the two. Subchondral bone, with its relatively greater stiffness and strength, provides mechanical support to the overlying cartilage and absorbs much of the mechanical force transmitted through the joint. Mechanical instability in osteoarthritic joints is thought to be a significant risk-factor in joint disease, due to the mechano-sensitive nature of many of its native tissues. Although the progression of joint disease remains incompletely understood, significant changes in subchondral bone remodelling, structure, composition, and mechanical properties have been documented in animal and human studies of OA. The purpose of this review is to explore and discuss these bony changes associated with disease and, in particular, contextualise the basic science and clinical literature on the role of subchondral bone in OA.

Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease-modifying activity

Chronic pancreatitis (CP), a progressive inflammatory disease, poses diagnostic challenges due to its initially asymptomatic nature. While CP’s impact on exocrine and endocrine functions is well-recognized, its potential influence on other body systems, particularly in young individuals, remains underexplored. This study investigates the hypothesis that CP in growing pigs leads to alterations in articular cartilage and subchondral bone, potentially contributing to osteoarthritis (OA) development. Utilizing a pig model of cerulein-induced CP, we examined the structural and compositional changes in subchondral bone, articular cartilage, and synovial fluid. Histological analyses, including Picrosirius Red and Safranin-O staining, were employed alongside immuno-histochemistry and Western blotting techniques. Our findings reveal significant changes in the subchondral bone, including reduced bone volume and alterations in collagen fiber composition. Articular cartilage in CP pigs exhibited decreased proteoglycan content and alterations in key proteins such as MMP-13 and TGF-β1, indicative of early cartilage degradation. These changes suggest a link between CP and musculoskeletal alterations, underscoring the need for further research into CP’s systemic effects. Our study provides foundational insights into the relationship between CP and skeletal health, potentially guiding future pediatric healthcare strategies for early CP diagnosis and management.

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 common degenerative disease that affects the musculoskeletal structure of the whole joint, which is characterized by progressive destruction of both articular cartilage and subchondral bone. Treatment of the bone pathologies, particularly osteoclast‐mediated subchondral bone loss in the early stages of OA, could prevent subsequent cartilage degeneration and progression of OA. In the present study, the PKC inhibitor, Sotrastaurin, was found to inhibit RANKL‐induced osteoclast formation in vitro in a dose‐ and time‐dependent manner. In particular, SO exerted its anti‐osteoclastic effect predominantly at the early stages of RANKL stimulation, suggesting inhibitory effects on precursor cell fusion. Using mature osteoclasts cultured on bovine bone discs, we showed that SO also exerts anti‐resorptive effects on mature osteoclasts bone resorptive function. Mechanistically, SO attenuates the early activation of the p38, ERK and JNK signalling pathways, leeding to impaired induction of crucial osteoclast transcription factors c‐Jun, c‐Fos and NFATc1. We also showed that SO treatment significantly inhibited the phosphorylation of PKCδ and MARCKS, an upstream regulator of cathepsin K secretion. Finally, in animal studies, SO significantly alleviates the osteochondral pathologies of subchondral bone destruction as well as articular cartilage degeneration following DMM‐induced OA, markedly improving OARSI scores. The reduced subchondral bone loss was associated with marked reductions in TRAP(+) osteoclasts in the subchondral bone tissue. Collectively, our data provide evidence for the protective effects of SO against OA by preventing aberrant subchondral bone and articular cartilage changes. Thus, SO demonstrates potential for further development as an alternative therapeutic option against OA.

Transforming growth factor β (TGFβ) signaling plays a complex tissue-specific and nonlinear role in osteoarthritis (OA). This study was conducted to determine the osteocytic contributions of TGFβ signaling to OA. To identify the role of osteocytic TGFβ signaling in joint homeostasis, we used 16-week-old male mice (n = 9-11 per group) and female mice (n = 7-11 per group) with an osteocyte-intrinsic ablation of TGFβ receptor type II (TβRIIocy-/- mice) and assessed defects in cartilage degeneration, subchondral bone plate (SBP) thickness, and SBP sclerostin expression. To further investigate these mechanisms in 16-week-old male mice, we perturbed joint homeostasis by subjecting 8-week-old mice to medial meniscal/ligamentous injury (MLI), which preferentially disrupts the mechanical environment of the medial joint to induce OA. In all contexts, independent of sex, genotype, or medial or lateral joint compartment, increased SBP thickness and SBP sclerostin expression were spatially associated with cartilage degeneration. Male TβRIIocy-/- mice, but not female TβRIIocy-/- mice, had increased cartilage degeneration, increased SBP thickness, and higher levels of SBP sclerostin compared with control mice (all P < 0.05), demonstrating that the role of osteocytic TGFβ signaling on joint homeostasis is sexually dimorphic. With changes in joint mechanics following injury, control mice had increased SBP thickness, subchondral bone volume, and SBP sclerostin expression (all P < 0.05). TβRIIocy-/- mice, however, were insensitive to subchondral bone changes with injury, suggesting that mechanosensation at the SBP requires osteocytic TGFβ signaling. Our results provide new evidence that osteocytic TGFβ signaling is required for a mechanosensitive response to injury, and that osteocytes control SBP homeostasis to maintain cartilage health, identifying osteocytic TGFβ signaling as a novel therapeutic target for OA.