Background/Purpose: The destabilisation of the medial meniscus (DMM) mouse osteoarthritis (OA) model is commonly used to study OA joint degeneration. In DMM-OA, the knee is destabilised by transecting the medial-meniscotibial ligament, resulting in increased loading on the medial tibial compartment. Similar to human OA, this leads to articular cartilage damage, subchondral bone accrual and osteophyte formation. We conducted a longitudinal study to define temporal changes in tibial bone structure and cartilage integrity in this model.

Methods: 12-week old male C57BL/6 mice underwent DMM or sham surgery on the right knee; left knees served as contra-lateral controls. In vivo micro-CT was performed prior to surgery, and 4, 8, 12 weeks post-surgery. NRecon and CT-Analyser (Skyscan) were used for micro-CT data reconstruction and analysis; the latter was performed using a novel approach specifically developed for assessing bone of varying mineralisation states. Histologic assessment of cartilage damage was performed using the OARSI scoring matrix for mouse models of osteoarthritis.  Statistics: 2-way ANOVA, Bonferroni post-hoc tests. Baseline bone volume/tissue volumes (BV/TV) and bone mineral density were similar in all limbs.

Results: Consistent with an increase in loading, micro-CT analyses demonstrated focal increases in medial subchondral bone in DMM-OA tibiae; BV/TV and bone mineral density were significantly increased at this site compared to sham from 4 weeks post-surgery (p<0.001). In contrast, the lateral subchondral bone BV/TV did not differ between DMM-OA and sham tibiae and the tibial trabecular BV/TV was similar in all limbs, indicating no systemic effects of DMM-OA on bone remodelling. Histologic assessment demonstrated proteoglycan loss in medial articular cartilage in DMM-OA tibiae from 4 weeks post-surgery, with cartilage erosion evident by 8 weeks post-surgery. Interestingly, medial subchondral bone BV/TV was similar between DMM-OA tibiae and their contra-lateral tibiae, suggesting alterations in gait may affect the subchondral bone structure in the contra-lateral knee; an observation also made in human OA.  Articular cartilage was intact in these contra-lateral tibiae.

Conclusion: In summary, focal changes in subchondral bone structure occur early in DMM-OA in response to joint destabilisation, and precede proteoglycan loss and erosion of the articular cartilage. Altered bone structure in contra-lateral tibiae of DMM-OA mice, suggests that increased subchondral bone alone, does not necessarily impact overlying articular cartilage integrity, and also serves to highlight the need to include sham-operated mice when using this model.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/changes-in-tibial-bone-and-cartilage-structure-in-a-mouse-surgical-model-of-osteoarthritis/