Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis

Abstract

Background:The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA.Methods:A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively.Results:Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks.Conclusion:The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed.

Characterization of OA development between sexes in the rat medial meniscal transection model

“…However, no differences were noted for either volume or thickness parameters, even when accounting for weight. While increased bone mineral density was observed in the current study, previous studies involving the male MMT models have demonstrated that significant morphological changes in the subchondral bone tend to emerge at later time points 47 .…”

Contrast enhanced μCT imaging of early articular changes in a pre-clinical model of osteoarthritis

“…Subchondral bone thickening and changes in mineral density are known to occur early in human OA and to be evident before radiographic indications of joint space narrowing 33,34 . In a previous study by Yu et al, MMT resulted in increases in subchondral plate thickness and decreases in plate mineral density within the medial tibial plateau at 8-and 12-weeks post-surgery 35 . In the current study, however, there were significant increases in mineral density, volume, and thickness in the subchondral bone at 3-weeks postsurgery.…”

Validation of the Diagnostic and Prognostic Values of ADAMTS5 and FSTL1 in Osteoarthritis Rat Model

“…In the first group (the OA group), 24 rats were subjected to unilateral MMT surgery on the right knee joint. 19,20 Briefly, each rat was anesthetized by intraperitoneal injection of pentobarbital (50 mg/kg), and the anterior portion of the right knee was shaved and sterilized. The surgery was achieved under a dissecting microscope.…”

“…The present study was conducted to determine the usefulness of ADAMTS5 and FSTL1 as potential biomarkers of OA using medial meniscal tear (MMT) surgery in rats, which were previously used as a convenient model of OA. 13,18-20 We also endeavored to conduct the correlation between these 2 proteins with OA progression and with a set of conventional OA-related inflammatory markers, including TNF-α, CRP, and ESR. 5-7…”