Adipocytes exert lipotoxic effects on osteoblast through activating hypoxia signaling pathway in vitro

This study aimed to investigate the effect of adipocytes on osteoblastic bone formation in vitro. The differentiated and undifferentiated 3T3-L1 cells were co-cultured with primary calvarial osteoblasts. At 48 h, proliferated osteoblasts decreased significantly after co-culture with differentiated preadipocytes as compared to those co-cultured with undifferentiated preadipocytes; at 7 days, the expressions of bone formation-related genes decreased in osteoblasts co-cultured with differentiated preadipocytes; at 14 days, osteoblasts mineralization also decreased significantly after co-culture with differentiated preadipocytes. To further determine whether the decreased proliferation and mineralization were related to the hypoxia signaling pathway, the expressions of hypoxia related-genes were detected. Results showed the expressions of these genes significantly increased after co-culture with differentiated preadipocytes. NF-κB and IL-6 expressions were also up-regulated in osteoblasts co-cultured with differentiated preadipocytes. Osteoblasts from Hif1α(f/f) mice showed increased proliferation and mineralization after co-culture with adipocytes transfected with adenoviral-cre, accompanied by up-regulated expressions of bone formation-related genes and down-regulated expressions of NF-κB and IL-6. These results demonstrated that adipocytes exert a negative effect on the proliferation and mineralization of osteoblasts via up-regulating the expressions of hypoxia-related genes, and NF-κB and IL-6 may impair the osteoblastic bone formation.