IADR Abstract Archives
Irisin Regulated Bone Metabolism in Gain-of- and Loss-of-function Mouse Models
Objectives: To explore the effects of myokine irisin in bone formation and further establish irisin knockout mouse line to determine the mechanisms of irisin regulating bone metabolism.
Methods: (1) MC3T3-E1 and RAW264.7 cells were cultured with induction, and treated in the presence of irisin for 7, 10 and 14 days. (2) Irisin protein (3.24 ng/mouse) or saline (n=6) were injected Intraperitoneal (IP) daily for 14 days. (3) We created C57BL/6 mice carrying irisin gene bordered with two loxP sequences (irisinfl/fl). Irisin conditional knockout (cKO) mice were generated by crossing irisinfl/fl mice with Sp7-Cre mice, the transgenic mice expressing Cre recombinase gene specifically in osteoblastic lineage. Micro-CT scanning was performed on cKO and wild-type (WT) group (n=4) on 6 and 10 weeks.
Results: (1) Irisin increased osteoblast differentiation and nuclear levels of β-catenin in MC3T3-E1 preosteoblastic cells, and reduced osteoclastogenesis by inhibiting NFATc1 expression in RANKL-treated RAW264.7 cells. (2) IP injections of recombinant irisin increased the presence of osteoblasts at the edge of the growth plate and enhanced irisin levels in serum. Micro-CT analyses of femur revealed significant increases in bone volume and thickness. (3) Mineralization of skull, hyoid, ribs, xiphoid and coccyx in cKO group were significantly slower than in WT group at 6 and 10 weeks. (4) Co.BMD and Tb.BV/TV in femurs in cKO group were significantly lower than in WT group, while the Co.BS/BV were increased (p < 0.05).
Conclusions: Our studies for the first time demonstrated that irisin increased osteoblastogenesis through the Wnt/b-catenin pathway and inhibited osteoclastogenesis by suppressing the RANKL/NFATc1 pathway. Irisin systemic administration increased trabecular bone volume, cortical bone thickness, and osteoblast numbers. Our newly established irisin cKO mice showed delayed bone formation and mineralization. Irisin, as a new myokine, may play an important role in bone metabolism, representing a potential molecule for prevention and treatment of bone diseases.
Methods: (1) MC3T3-E1 and RAW264.7 cells were cultured with induction, and treated in the presence of irisin for 7, 10 and 14 days. (2) Irisin protein (3.24 ng/mouse) or saline (n=6) were injected Intraperitoneal (IP) daily for 14 days. (3) We created C57BL/6 mice carrying irisin gene bordered with two loxP sequences (irisinfl/fl). Irisin conditional knockout (cKO) mice were generated by crossing irisinfl/fl mice with Sp7-Cre mice, the transgenic mice expressing Cre recombinase gene specifically in osteoblastic lineage. Micro-CT scanning was performed on cKO and wild-type (WT) group (n=4) on 6 and 10 weeks.
Results: (1) Irisin increased osteoblast differentiation and nuclear levels of β-catenin in MC3T3-E1 preosteoblastic cells, and reduced osteoclastogenesis by inhibiting NFATc1 expression in RANKL-treated RAW264.7 cells. (2) IP injections of recombinant irisin increased the presence of osteoblasts at the edge of the growth plate and enhanced irisin levels in serum. Micro-CT analyses of femur revealed significant increases in bone volume and thickness. (3) Mineralization of skull, hyoid, ribs, xiphoid and coccyx in cKO group were significantly slower than in WT group at 6 and 10 weeks. (4) Co.BMD and Tb.BV/TV in femurs in cKO group were significantly lower than in WT group, while the Co.BS/BV were increased (p < 0.05).
Conclusions: Our studies for the first time demonstrated that irisin increased osteoblastogenesis through the Wnt/b-catenin pathway and inhibited osteoclastogenesis by suppressing the RANKL/NFATc1 pathway. Irisin systemic administration increased trabecular bone volume, cortical bone thickness, and osteoblast numbers. Our newly established irisin cKO mice showed delayed bone formation and mineralization. Irisin, as a new myokine, may play an important role in bone metabolism, representing a potential molecule for prevention and treatment of bone diseases.
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