Figure 3. Ciliary signaling in cartilage and bone cells.

Articular chondrocytes sense mechanical forces including shear stress, rotation, pressure, and tension in part through interactions of the ECM with ciliary integrins and NG2 chondroitin sulfate proteoglycan [10,43,113] with responses supporting development of tissue anisotropy. In load-bearing areas of the bone, cilia of nonproliferative superficial cells at the articular surface projecting away from the surface, whereas columns of proliferating cells (e.g. like growth plate chondrocytes) can be oriented towards or away from the articular surface [11,43,45]. A compression-induced Ca²⁺ signaling response mediated by ATP release relies on cilia integrity [44]. Hydrostatic loading of growth plate chondrocytes increases Indian hedgehog (IHH) signaling, governing chondrocyte proliferation and differentiation in the growth plate dependent on intact cilia [114]. Cilia are required for osteogenic and bone resorptive responses to fluid flow, but in contrast to other tissues, these responses do not require Ca²⁺ [52]. In osteocytes, fluid flow leads to a decrease of cAMP dependent on ciliary AC6, which induces COX-2 gene expression [51]. Paracrine signaling by mechanically stimulated osteocytes relies on cilia [53].