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 ske...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 osteoblasts,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 osteoblasts,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.
