Figure 1. Regulation of osteoclast development by RANKL and other cytokines in the bone marrow microenvironment.

Modified from Riggs et al. with permission ²². Remodeling begins with the elaboration of cytokines from osteoblast precursors leading to the recruitment and differentiation of multinucleated osteoclasts that subsequently attach to the endosteal bone surface. Resorption of the skeletal matrix releases growth factors such as IGF-I and TFG-beta which recruit lining cells and early osteoblast precursors that eventually form new bone. Osteoblasts that do not undergo programmed cell death are entombed within the skeletal matrix and become osteocytes that can signal lining cells and respond to gravitary forces to initiate remodeling.] <Added on page 5>