title: Insulin-like growth factor-I is essential for embryonic bone development.
abstract: Although IGF-I has been identified as an important growth factor for the skeleton, the role of IGF-I on embryonic bone development remains unknown. Here we show that, in IGF-I-deficient (IGF-I(-/-)) mice, skeletal malformations, including short-limbed dwarfism, were evident at days post coitus (dpc) 14.5 to 18.5, accompanied by delays of mineralization in the spinal column, sternum, and fore paws. Reduced chondrocyte proliferation and increased chondrocyte apoptosis were identified in both the spinal ossification center and the growth plate of long bones. Abnormal chondrocyte differentiation and delayed initiation of mineralization was characterized by small size and fewer numbers of type X collagen expressing hypertrophic chondrocytes and lower osteocalcin expression. The Indian hedgehog-PTHrP feedback loop was altered; expression of Indian hedgehog was reduced in IGF-I(-/-) mice in long bones and in the spine, whereas expression of PTHrP was increased. Our results indicate that IGF-I plays an important role in skeletal development by promoting chondrocyte proliferation and maturation while inhibiting apoptosis to form bones of appropriate size and strength.
authors.affiliation: Department of Medicine, Endocrine Unit, 111N, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, California 94121, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nishida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakata
authors.forename: Hashem Z
authors.initials: HZ
authors.lastname: Elalieh
authors.forename: Wenhan
authors.initials: W
authors.lastname: Chang
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Halloran
authors.forename: Steven B
authors.initials: SB
authors.lastname: Doty
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Bikle
mesh_terms: D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000196:embryology*; D002113:Calcification, Physiologic / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D019902:Chondrocytes / Q000502:physiology / Q000648:ultrastructure; D024043:Collagen Type II / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D024043:Collagen Type II; D044162:Parathyroid Hormone-Related Protein; D007334:Insulin-Like Growth Factor I