Review Question - QID 3088

RANKL, a key osteoclastogenic protein, is expressed by osteoblasts and binds to the RANK receptor on osteoclast precursor cells.

The binding of RANKL to RANK on osteoclast precursor cells drives their differentiation into mature osteoclasts (multinucleated giant cells). Mature osteoclasts bind to the bone surfaces via integrins and resorb bone via their ruffled border within Howship's lacunae. Osteocytes orchestrate bone resorption and bone deposition by controlling osteoclast and osteoblast activity. Osteoblasts release RANKL to induce osteoclast differentiation, while osteoblasts release osteoprotegerin (OPG) to downregulate osteoclastogenesis. Osteocytes also release fibroblast growth factor-23 (FGF-23), BMPs and sclerostin to regulate osteoblast activity. Antibodies to RANKL and Sclerostin have both been shown to increase bone density.

Compton et al. reviewed osteocyte function and the emerging importance of sclerostin, which is a glycoprotein. Sclerostin is predominantly secreted by osteocytes under physiologic conditions to act as an important negative regulator of bone mass through inhibition of bone formation by osteoblasts.

Illustration A demonstrates local bone milieu. It depicts the interplay between osteocytes, osteoblasts, and osteoclasts via the factors described above.

Incorrect answers:
Answer 1: RANKL is not expressed by osteoclasts, its expression leads to osteoclast differentiation and activation.
Answer 3: Integrins are transmembrane receptors that allow mature osteoclasts to bind to the surface of bones. They do not express RANKL.
Answer 4: RANKL is expressed by T helper cells and is thought to be involved in dendritic cell maturation.
Answer 5: RANKL is not known to be expressed by macrophages.