Figure 2.

Cellular targets in subchondral bone remodeling. (A) Subchondral bone remodeling in OA (as illustrated in the knee). Cells and cellular structures depicted include MSCs (B), osteoclasts (C), osteoblasts (D), osteocytes (E), and blood vessels and nerves (F). Increased osteoclast-mediated subchondral bone resorption (depicted by the large lacuna formed) at the onset of OA results in the release of growth factors previously embedded in bone ECM into the subchondral bone marrow. Subsequent actions of these factors, such as TGFβ contribute to angiogenesis, nerve innervation, and recruitment of MSCs and osteoprogenitors. These cellular processes together lead to activated bone formation, uncoupled bone remodeling, and disruption of the subchondral bone architecture. These alterations in the subchondral bone impair its mechanical properties of subchondral bone, such as load dissipation, and contribute to degeneration of articular cartilage. Current therapeutics, potential targets and potential therapies for subchondral bone remodeling are shown for: (B) MSCs, (C) osteoclasts, (D) osteoblasts, (E) osteocytes, and (F) blood vessels and nerves.