Journal of cellular and molecular medicine
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The anaphylatoxin C5a is generated upon activation of the complement system, a crucial arm of innate immunity. C5a mediates proinflammatory actions via the C5a receptor C5aR1 and thereby promotes host defence, but also modulates tissue homeostasis. There is evidence that the C5a/C5aR1 axis is critically involved both in physiological bone turnover and in inflammatory conditions affecting bone, including osteoarthritis, periodontitis, and bone fractures. ⋯ Interestingly, using coimmunoprecipitation, we found an interaction between C5aR1 and Toll-like receptor 2 (TLR2) in osteoblasts. The C5aR1- and TLR2-signalling pathways converge on the activation of p38 MAPK and the generation of C-X-C motif chemokine 10, which functions, among others, as an osteoclastogenic factor. In conclusion, C5a-stimulated osteoblasts might modulate osteoclast activity and contribute to immunomodulation in inflammatory bone disorders.