title: Adipocytes exert lipotoxic effects on osteoblast through activating hypoxia signaling pathway in vitro.
abstract: 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.
authors.affiliation: Department of Endocrinology, Shanghai Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Shanghai Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Shanghai Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Endocrinology, Shanghai Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Shan
authors.affiliation: Department of Endocrinology, Shanghai Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, Shanghai Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Lige
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Endocrinology, Shanghai Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Zhang
keywords: 3T3L1 cells; Co-culture; adipocytes; hypoxia signaling pathway; osteoblasts