Bone Abstracts

It has long been known that osteoarthritis induces dramatic structural changes in subchondral bone. Studies on patients’ biopsies have also shown that the new sclerotic bone is hypomineralized and has decreased elastic modulus. Due to their amenability for genetic studies, murine models of OA are particularly important for drug target discovery. However, whilst osteosclerosis has been reported also in murine OA models, little is known about the compositional and mechanical properties of mouse subchondral bone (SCB). In this study we assessed microstructure, mineralization and nanomechanical properties of SCB in the surgical destabilization of medial meniscus (DMM) model of OA.

Six groups of C57BL/6 mice (n=6) underwent DMM surgery and were euthanized 1, 2, 4, 8, 12 and 20 weeks post-surgery. Tibiae were imaged in a BMD calibrated microCT scanner (Skyscan 1172), embedded in methyl methacrylate blocks and cut in half coronally. The surface of the block halves was polished and subjected to nanoindentation test (TI700 UBI indenter, Hysitron, MN, USA) using a Berkovich probe. Nanomechanical properties were extracted from load-displacement curves using Oliver-Pharr method.

Structural analysis by microCT (5 μm/pixel resolution) revealed SCB plate sclerosis and trabecular bone remodelling from 2 weeks post-surgery in the medial condyle of the DMM-operated tibiae and no changes in the lateral condyle. However, volumetric BMD was unaltered in both SCB compartments. Initial nanoindentation data (on tibiae from 4 weeks post-DMM) showed no changes in either bone elastic modulus or hardness.

This suggests the existence of a different compositional and nanomechanical environment in mouse SCB compared to human SCB with the progression of OA. A different SCB environment might explain some of the differences in OA pathogenesis in the mouse compared to human and should be further investigated in order to address one potential limitation of the murine DMM model of OA.