The MCP-3/Ccr3 axis contributes to increased bone mass by affecting osteoblast and osteoclast differentiation

초록

Several CC subfamily chemokines have been reported to regulate bone metabolism by affecting osteoblast or osteoclast differentiation. However, the role of monocyte chemotactic protein 3 (MCP-3), a CC chemokine, in bone remodeling is not well understood. Here, we show that MCP-3 regulates bone remodeling by promoting osteoblast differentiation and inhibiting osteoclast differentiation. In a Ccr3-dependent manner, MCP-3 promoted osteoblast differentiation by stimulating p38 phosphorylation and suppressed osteoclast differentiation by upregulating interferon beta. MCP-3 increased bone morphogenetic protein 2-induced ectopic bone formation, and mice with MCP-3-overexpressing osteoblast precursor cells presented increased bone mass. Moreover, MCP-3 exhibited therapeutic effects by abrogating receptor activator of nuclear factor kappa-B ligand-induced bone loss. Therefore, MCP-3 has therapeutic potential for diseases involving bone loss due to its positive role in osteoblast differentiation and negative role in osteoclast differentiation. Our bones are always changing, needing a balance between bone creation and bone breakdown. Researchers investigates how a specific protein, MCP-3, affects this balance. They found that MCP-3 promotes the creation of osteoblasts and stops the creation of osteoclasts. The study involved both in vitro and in vivo methods, looking at how changing MCP-3 levels impacts bone change processes. Researchers found that increasing MCP-3 levels in bone-making cells resulted in stronger bones in mice, suggesting MCP-3 is key in promoting bone creation and stopping excessive bone loss. This was partly due to MCP-3's interaction with specific cell receptors and signaling pathways that affect bone cell activity. This research paves the way for future studies on MCP-3 as a target for bone-strengthening therapies, potentially leading to new treatments for diseases that weaken bones. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

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