Comparison of subchondral bone microarchitectures in rat osteoarthritis models under different trauma mechanisms

To compare the progression of articular cartilage lesions and subchondral bone microstructural alterations at different postoperative time points among three rat models of osteoarthritis (OA), and to facilitate the selection of OA animal models in research.

Sixty-four male Sprague-Dawley rats were randomly assigned to four groups (n=16 per group): a sham group, anterior cruciate ligament transection (ACLT) group, conventional Hulth group , and a group subjected to the conventional Hulth procedure combined with intra-articular sodium iodoacetate injection (Hulth+iodoacetate). Knee joint specimens were harvested at 4 and 8 weeks postoperatively for gross observation and micro-computed tomography (micro-CT). Bone microstructural parameters, including the bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and structure model index (SMI), were quantified via micro-CT analysis. Cartilage structure was observed under light microscopy.

In each of the model groups, OA phenotypes of varying severity were induced. At 4 weeks postoperatively, roughened articular surfaces, periarticular tissue hyperplasia, and early-stage cartilage damage were detected in the ACLT and Hulth model groups, concurrent with reduced subchondral bone mass and associated osteoporotic changes. At week 8, the disease progressed to the middle and late stages, characterized by severe uneven joint surfaces and the formation of mature osteophytes in the ACLT and Hulth model groups. In the Hulth+iodoacetate group, pathological features of late-stage OA appeared as early as 4 weeks postoperatively. There was extensive cartilage defect with erosion of the subchondral bone. Compared with the sham group, BV/TV and Tb.N were significantly reduced while SMI and Tb.Sp were significantly increased in the Hulth+iodoacetate group (P < 0.05).

Progressive degeneration from early to advanced stages of OA has been recapitulated in the ACLT and Hulth model groups over the 4-8 week period, whereas a severe and highly reproducible OA phenotype can be rapidly induced in the Hulth+iodoacetate model group. Subchondral bone loss, microstructural degeneration, and abnormal bone remodeling have been induced in all model groups.