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Could C3a be the coupling factor between bone resorption and formation?
DOI:10.1038/bonekey.2014.49
Searching for factors involved in this elusive coupling mechanism, Matsuoka et al. co-cultured mature osteoclasts with bone marrow macrophage-derived pre-osteoclasts in the presence of increased levels of RANKL, showing that osteoblastogenesis of the latter was promoted.
The condition medium from mature osteoclasts was then investigated to try to identify the source of bioactivity. This revealed that osteoclast expression of the complement component C3a rose during osteoclast differentiation. C3a from the condition medium was also shown to stimulate alkaline phosphatase activity in the pre-osteoblasts.
In vivo studies confirmed that the C3 gene was expressed at a significantly higher level in ovariectomized (OVX) mice compared to sham-operated controls. Treatment of OVX mice with SB290157, a specific antagonist for the C3a receptor, for 6 days after surgery led to a significant increase in bone formation. The authors conclude that C3a produced by osteoclasts binds to the C3a receptor on pre-osteoblasts, providing the coupling link between bone resorption and formation.
Editor’s comment: This study demonstrates that mature osteoclasts secrete C3a, which acts by binding to its receptor C3aR on osteoblasts to enhance osteoblastogenesis. The relationship and relative roles of osteoclast-derived coupling factors identified thus far, including ephrinB2, Cthrc1, S1P and C3a, remains to be clarified.
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