Insulin-like growth factor-I （IGF-I） regulates cell growth, survival, and differentiation by acting on the IGF-I receptor, （IGF-IR）-a tyrosine kinase receptor, which elicits diverse intracellular signaling respons...Insulin-like growth factor-I （IGF-I） regulates cell growth, survival, and differentiation by acting on the IGF-I receptor, （IGF-IR）-a tyrosine kinase receptor, which elicits diverse intracellular signaling responses. All skeletal cells express IGF-I and IGF-IR. Recent studies using tissue/cell-specific gene knockout mouse models and cell culture techniques have clearly demonstrated that locally produced IGF-I is more critical than the systemic IGF-I in supporting embryonic and postnatal skeletal development and bone remodeling. Local IGF-I/IGF-IR signaling promotes the growth, survival and differentiation of chondrocytes and osteo- blasts, directly and indirectly, by altering other autocrine/paracrine signaling pathways in cartilage and bone, and by enhancing interactions among these skeletal cells through hormonal and physical means. Moreover, local IGF-I/IGF-IR signaling is critical for the anabolic bone actions of growth hormone and parathyroid hormone. Herein, we review evidence supporting the actions of local IGF-I/IGF-IR in the above aspects of skeletal development and remodeling.展开更多
基金supported by NIH grants RO1 AG021353(W.C.),AR055924(D.B),DK 054793(D.B.)Department of Veteran Affairs Program Project Award Program in Bone Disease and Merit Review Grants(W.C.,D.B.)
文摘Insulin-like growth factor-I （IGF-I） regulates cell growth, survival, and differentiation by acting on the IGF-I receptor, （IGF-IR）-a tyrosine kinase receptor, which elicits diverse intracellular signaling responses. All skeletal cells express IGF-I and IGF-IR. Recent studies using tissue/cell-specific gene knockout mouse models and cell culture techniques have clearly demonstrated that locally produced IGF-I is more critical than the systemic IGF-I in supporting embryonic and postnatal skeletal development and bone remodeling. Local IGF-I/IGF-IR signaling promotes the growth, survival and differentiation of chondrocytes and osteo- blasts, directly and indirectly, by altering other autocrine/paracrine signaling pathways in cartilage and bone, and by enhancing interactions among these skeletal cells through hormonal and physical means. Moreover, local IGF-I/IGF-IR signaling is critical for the anabolic bone actions of growth hormone and parathyroid hormone. Herein, we review evidence supporting the actions of local IGF-I/IGF-IR in the above aspects of skeletal development and remodeling.
