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Role of Osteocyte-derived Insulin-Like Growth Factor I in Developmental Growth, Modeling, Remodeling, and Regeneration of the Bone

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초록

The osteocyte has long been considered to be the primary mechanosensory cell in thebone. Recent evidence has emerged that the osteocyte is also a key regulator of variousbone and mineral metabolism and that its regulatory effects are in part mediatedthrough locally produced osteocyte-derived factors, such as sclerostin, receptor activa-tor of nuclear factor-kappa B ligand (RANKL), and fibroblast growth factor (FGF)-23. Os-teocytes secrete large amounts of insulin-like growth factor (IGF)-I in bone. AlthoughIGF-I produced locally by other bone cells, such as osteoblasts and chondrocytes, hasbeen shown to play important regulatory roles in bone turnover and developmentalbone growth, the functional role of osteocyte-derived IGF-I in the bone and mineral me-tabolism has not been investigated and remains unclear. However, results of recentstudies in osteocyte Igf1 conditional knockout transgenic mice have suggested potentialregulatory roles of osteocyte-derived IGF-I in various aspects of bone and mineral me-tabolism. In this review, evidence supporting a regulatory role for osteocyte-derivedIGF-I in the osteogenic response to mechanical loading, the developmental bonegrowth, the bone response to dietary calcium depletion and repletion, and in fracturerepair is discussed. A potential coordinated regulatory relationship between the effect ofosteocyte-derived IGF-I on bone size and the internal organ size is also proposed.

Abstract

The osteocyte has long been considered to be the primary mechanosensory cell in thebone. Recent evidence has emerged that the osteocyte is also a key regulator of variousbone and mineral metabolism and that its regulatory effects are in part mediatedthrough locally produced osteocyte-derived factors, such as sclerostin, receptor activa-tor of nuclear factor-kappa B ligand (RANKL), and fibroblast growth factor (FGF)-23. Os-teocytes secrete large amounts of insulin-like growth factor (IGF)-I in bone. AlthoughIGF-I produced locally by other bone cells, such as osteoblasts and chondrocytes, hasbeen shown to play important regulatory roles in bone turnover and developmentalbone growth, the functional role of osteocyte-derived IGF-I in the bone and mineral me-tabolism has not been investigated and remains unclear. However, results of recentstudies in osteocyte Igf1 conditional knockout transgenic mice have suggested potentialregulatory roles of osteocyte-derived IGF-I in various aspects of bone and mineral me-tabolism. In this review, evidence supporting a regulatory role for osteocyte-derivedIGF-I in the osteogenic response to mechanical loading, the developmental bonegrowth, the bone response to dietary calcium depletion and repletion, and in fracturerepair is discussed. A potential coordinated regulatory relationship between the effect ofosteocyte-derived IGF-I on bone size and the internal organ size is also proposed.

참고문헌 (95)

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