Question

RANKL is:

A. expressed on osteoclasts

B. necessary for osteoclast development

C. suppressive of apoptosis

Answer 1

RANKL is:

expressed on osteoclasts,

The functional activity of osteoblasts and osteoclasts is synergistic and an imbalance may result in a variety of diseases, including osteoporosis. Osteoblasts regulate osteoclasts via the receptor activator of nuclear factor κ-B ligand (RANKL)-receptor activator of nuclear factor κ-B (RANK) signaling pathway.

RANKL is a transmembrane protein expressed on the surface of osteoblasts that can be shed from the plasma membrane by osteoclast-derived MMP-7

• RANKL is found to be highly upregulated within the first 24 h of fracture healing.
• This finding seems to contradict the primary role of RANKL as an inducer of osteoclastogenesis and a marker of bone remodeling.
• Early RANKL expression plays an important role in regulation of immunologic response, specifically maturation and proliferation of T helper cells, although little data exist to define its specific function.
• Experiments in RANKL knockout animals have shown that RANK/RANKL interaction within the immunologic niche is essential for activation of Th cells, and maintenance of the local dendritic cell population.
• In regards to RANKL’s early effect on the mesenchymal cell population, osteoprotegerin (OPG) is also found to be highly expressed during the same time period, likely negating RANKL’s effect on osteoclast precursors, via competitive inhibition of RANK.