Osteoclastogenesis

Osteoclasts derive from monocytes and macrophages. As we’ll see, numerous monocytes and macrophages will essentially merge to form a single osteoclast. These monocytes/macrophages differentiate in osteoclasts, they have many intermediary steps, which we can simplify into what we call preosteoclasts – essentially they are “on the road” to becoming an osteoclast. There are a variety of inciting events that stimulate osteoclastogenesis. From a physiological standpoint, parathyroid hormone (PTH) stimulates osteoblasts to secrete factors that promote osteoclastogenesis. Note that Vitamin D also triggers this process and has other calcium absorption activities but we’ll focus on PTH, here. Osteocyte distress and cell death (apoptosis) can trigger osteoclastogenesis via communication with osteoblasts on the bone surface.

• As we can imagine, if bone dies or is under stress and requires remodeling, it is important that osteocytes can signal for this change to happen.

Osteoblast release of M-CSF and RANKL are the two most notably activators of osteoclastogenesis. Osteoblasts release RANKL (a TNF-family ligand), which binds RANK on preosteoclasts to stimulate their differentiation into osteoclasts. During osteoclastogenesis inhibition, osteoprotegerin (OPG), instead, is released. OPG serves as a decoy receptor that RANKL binds to making it unable to bind to RANK (competitive inhibition). OPG avoids perpetual RANKL activation of RANK. Osteoblasts release M-CSF (macrophage colony stimulating factor), which stimulates preosteoclast differentiation and fusion into multinucleated osteoclasts (numerous preosteoclasts fuse to form a single osteoclast). A single osteoclast can contain 30 or more nuclei. Osteoclasts form a dome-shaped, multinucleated osteoclast with a ruffled border sealed to bone. To learn more, see: Osteoclasts