Thrombin inhibits osteoclast differentiation

Osteoclasts and osteoblasts are the major bone cells. Osteoblasts and their precursors express two factors that are essential for osteoclast differentiation and activity: M-CSF and RANKL. Factors that stimulate osteoclast differentiation, includie PTH, PGE2, 1,25-dihydroxyvitamin D3 (1,25D) and interleukin 6 (IL6), do so by stimulating an increase in the expression of RANKL relative to that of its soluble decoy receptor osteoprotegerin (OPG).

In the bone environment, active thrombin is generated upon initiation of blood coagulation as a result of bone fracture, as well as in rheumatoid arthritis and possibly other inflammatory conditions affecting. It is thus important to understand the full range of responses of bone cells elicited by this potent biological agent. The current study by Sivagurunathan et al. was initiated to investigate the hypothesis that thrombin-induced secretion of IL6 and PGE2 leads to an increase in the ratio of RANKL:OPG in osteoblastic cells and thus increased osteoclast differentiation in mixed populations of cells of the osteoblast and osteoclast lineages. When it was determined that, contrary to expectations, thrombin inhibits osteoclast differentiation induced by a variety of osteoclastogenic factors, further studies were undertaken to investigate the mechanism of the effect.

They found that although it has been known for many years that thrombin exerts pro-anabolic effects on cells of the osteoblast lineage, their results demonstrated for the first time that thrombin also exerts anti-catabolic effects on cells of the osteoclast lineage.

Read the full article in Sivagurunathan et al (2013) Journal of Molecular Endocrinology 50 347-359 DOI: 10.1530/JME-12-0177