Autocrine and Paracrine Actions of IGF-I Signaling in Skeletal Development.
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.
Endocrine Unit, University of California, San Francisco, Veterans Affairs Medical Center , San Francisco, CA, USA.
Yongmei
Y
Wang
Endocrine Unit, University of California, San Francisco, Veterans Affairs Medical Center , San Francisco, CA, USA.
Daniel D
DD
Bikle
Endocrine Unit, University of California, San Francisco, Veterans Affairs Medical Center , San Francisco, CA, USA.
Wenhan
W
Chang
CaSR; Calcium-sensing receptor; GH; IGF-I; IGF-IR; PTH; cell-cell communication; chondrocyte; osteoblast; osteoclast; signaling