Effect of aging on bone metabolism: the involvement of complement C1q

Purpose: impairment of normal bone remodeling affects the successful osseointegration of dental implants. Recently, it has been reported that complement C1q level increases with age and delays wound healing by modulating Wnt signaling. As Wnt signaling is known to play an essential role in bone remodeling, we hypothesized that aging-dependent increases in C1q affect bone remodeling. In this study, we examined whether C1q affects the differentiation of bone-forming osteoblasts and bone-resorting osteoclasts, and investigated whether C1q could modify cellular signaling, including the Wnt/beta-catenin pathway in these cells. Methods: Osteogenic differentiation of MC3T3-E1 cells was assessed using alkaline phosphatase staining. Differentiation of osteoclasts from mouse bone marrow cells was assessed using tartrate-resistant acid phosphatase staining. Activation of canonical Wnt signaling and protein phosphorylation was monitored using Western blotting. Results: C1q. at 5-15 mu g/mL promoted osteoclast fusion, whereas it did not affect the differentiation of osteoblasts. On the other hand, a higher concentration of C1q (50 mu g/mL) suppressed both bone morphogenetic protein-2-induced ostcogenic differentiation and osteoclast formation. C1q did not induce an obvious activation of Wnt/beta-catenin signaling in either pre-osteoblasts or pre-osteoclasts, contrary to previous reports using other tissues. Instead, C1q upregulated the receptor activator of nuclear factor-kappa 13 ligand (RANKL)-induced phosphorylation of Akt. Conclusions: C1q could affect cellular signaling and modify the differentiation of osteoblasts and osteoclasts. depending on the concentration. Therefore, an increase in C1q with age could be one of the factors that determine the prognosis of treatment of elderly patients.

Automated summary

The study found that C1q can affect the differentiation of osteoblasts and osteoclasts, depending on the concentration. C1q does not activate the Wnt/beta-catenin signaling pathway, but can upregulate RANKL-induced phosphorylation of Akt.