Characterisation of Growth Plate Dynamics in Murine Models of Osteoarthritis

Abstract

The purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics are associated with osteoarthritis development. 8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) (n = 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was confirmed by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to 3-dimensional (3D) growth plate bridging analysis. Higher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely expressed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes in DMM (p=0.002 and p<0.0001, respectively) and loaded (both p<0.0001) tibiae of mice compared to their controls. 3D quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints. The results confirm articular cartilage chondrocyte transiency in a surgical and loaded murine models of osteoarthritis. Herein, we reveal spatial variation of growth plate bridging in surgical and loaded osteoarthritis models and how these may contribute to anatomical variation in vulnerability of osteoarthritis development.

Collagen type X expression and chondrocyte hypertrophic differentiation during OA and OS development

“…The model can be used to study the effect of cyclic load on joint. In the study of OA growth plate dynamics, increased expression of COL10A1 and MMP13, markers of chondrocyte hypertrophy, were observed in articular cartilage and tibial growth plate in a mouse load model [11]. One study has shown that mechanical joint loading can be used as a suitable model to study mechanical OA pain, effectively avoiding the risk of postoperative pain and infection that may result from surgical intervention [84].…”

“…Articular cartilage is a layer of hyaline cartilage, mainly composed of ECM and resting chondrocytes, including collagen (Collagen II, VI, IX), hyaluronic acid and proteoglycan [9]. With the progression of OA, articular chondrocytes are activated, and the expression of articular cartilage related markers such as proteoglycan, type II collagen, are significantly down-regulated [10], while hypertrophic markers, including type X collagen, MMP13, and ADAMTS5, may become highly expressed in chondrocytes undergoing hypertrophic changes [11]. The abnormal hypertrophy of articular chondrocytes results in carti-lage matrix degradation, vascular invasion, and osteoid formation, mirroring the terminal differentiation of chondrocytes observed during endochondral bone formation [12].…”

Inhibition of Leukotriene A4 Hydrolase Suppressed Cartilage Degradation and Synovial Inflammation in a Mouse Model of Experimental Osteoarthritis

“…4,25 After that, all the animals were fed with the standard diet from the Animal Center (control diet) for at least 2 weeks as an observation period. Eight-week-old C57BL/6 mice (similar to other studies, [30][31][32] while 8-week-old of mice were considered as around 18-year-old in human age) 33 were randomly assigned and underwent destabilization of the medial meniscus (DMM) surgery to induce OA as previously described. 25 Briefly, OA was induced by dissecting the medial meniscus ligament to destabilize the medial meniscus in the knee joint of the hind limb on the right side.…”

DiaPASEF proteotype analysis indicates changes in cell growth and metabolic switch induced by caspase‐9 inhibition in chondrogenic cells

“…Recent lineage studies, supporting the presence of skeletal stem cells within cartilage make such research particularly challenging [1]. Growth plate chondrocytes are intensely investigated in basic research but also with respect to the spectrum of skeletal and metabolic disorders [2, 3]. Changes in chondrocyte behavior are associated also with osteoarthritis [4, 5], rheumatoid arthritis [6], and increased chondrocyte proliferation without a change in apoptosis was reported in osteoporosis [7].…”