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Role of IGFBP2, IGF-I and IGF-II in regulating long bone growth.
Bone. 2005 Dec; 37(6):741-50.BONE

Abstract

The IGF axis is important for long bone development, homeostasis and disease. The activities of IGF-I and IGF-II are regulated by IGF binding proteins (IGFBPs). IGF-I and IGFBP2 are co-expressed in dynamic fashions in the developing long bones of the chick wing, and we have found that IGF-II is present in the cartilage model and surrounding perichondrium, proliferative and hypertrophic chondrocytes and developing periosteum. To gain insight into endogenous roles of IGF-I, IGF-II and IGFBP2 in long bone development, we have overexpressed IGFBP2 in the developing skeletal elements of the embryonic chick wing in vivo, using an RCAS retroviral vector. IGFBP2 overexpression led to an obvious shortening of the long bones of the wing. We have investigated, at the cellular and molecular levels, the mechanism of action whereby IGFBP2 overexpression impairs long bone development in vivo. At an early stage, IGFBP2 excess dramatically inhibits proliferation by the chondrocytes of the cartilage models that prefigure the developing long bones. Later, IGFBP2 excess also reduces proliferation of the maturing chondrocytes and attenuates proliferation by the perichondrium/developing periosteum. IGFBP2 excess does not affect morphological or molecular indicators of chondrocyte maturation, osteoblast differentiation or cell/matrix turnover, such as expression of Ihh, PTHrP, type X collagen and osteopontin, or distribution and relative abundance of putative clast cells. We also have found that IGFBP2 blocks the ability of IGF-I and IGF-II to promote proliferation and matrix synthesis by wing chondrocytes in vitro. Together, our results suggest that the mechanism of action whereby IGFBP2 excess impairs long bone development is to inhibit IGF-mediated proliferation and matrix synthesis by the cartilage model; reduce the proliferation and progression to hypertrophy by the maturing chondrocytes; and attenuate proliferation and formation of the periosteal bony collar. These actions retard the growth and longitudinal expansion of the developing long bones, resulting in shortened wing skeletal elements. Our results emphasize the importance of a balance of IGF/IGFBP2 action at several stages during normal long bone development.

Authors+Show Affiliations

Center for Limb and Skeletal Development, Department of BioStructure and Function, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16183342

Citation

Fisher, Melanie C., et al. "Role of IGFBP2, IGF-I and IGF-II in Regulating Long Bone Growth." Bone, vol. 37, no. 6, 2005, pp. 741-50.
Fisher MC, Meyer C, Garber G, et al. Role of IGFBP2, IGF-I and IGF-II in regulating long bone growth. Bone. 2005;37(6):741-50.
Fisher, M. C., Meyer, C., Garber, G., & Dealy, C. N. (2005). Role of IGFBP2, IGF-I and IGF-II in regulating long bone growth. Bone, 37(6), 741-50.
Fisher MC, et al. Role of IGFBP2, IGF-I and IGF-II in Regulating Long Bone Growth. Bone. 2005;37(6):741-50. PubMed PMID: 16183342.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of IGFBP2, IGF-I and IGF-II in regulating long bone growth. AU - Fisher,Melanie C, AU - Meyer,Carissa, AU - Garber,Graham, AU - Dealy,Caroline N, Y1 - 2005/09/22/ PY - 2005/02/02/received PY - 2005/04/20/revised PY - 2005/07/05/accepted PY - 2005/9/27/pubmed PY - 2006/3/18/medline PY - 2005/9/27/entrez SP - 741 EP - 50 JF - Bone JO - Bone VL - 37 IS - 6 N2 - The IGF axis is important for long bone development, homeostasis and disease. The activities of IGF-I and IGF-II are regulated by IGF binding proteins (IGFBPs). IGF-I and IGFBP2 are co-expressed in dynamic fashions in the developing long bones of the chick wing, and we have found that IGF-II is present in the cartilage model and surrounding perichondrium, proliferative and hypertrophic chondrocytes and developing periosteum. To gain insight into endogenous roles of IGF-I, IGF-II and IGFBP2 in long bone development, we have overexpressed IGFBP2 in the developing skeletal elements of the embryonic chick wing in vivo, using an RCAS retroviral vector. IGFBP2 overexpression led to an obvious shortening of the long bones of the wing. We have investigated, at the cellular and molecular levels, the mechanism of action whereby IGFBP2 overexpression impairs long bone development in vivo. At an early stage, IGFBP2 excess dramatically inhibits proliferation by the chondrocytes of the cartilage models that prefigure the developing long bones. Later, IGFBP2 excess also reduces proliferation of the maturing chondrocytes and attenuates proliferation by the perichondrium/developing periosteum. IGFBP2 excess does not affect morphological or molecular indicators of chondrocyte maturation, osteoblast differentiation or cell/matrix turnover, such as expression of Ihh, PTHrP, type X collagen and osteopontin, or distribution and relative abundance of putative clast cells. We also have found that IGFBP2 blocks the ability of IGF-I and IGF-II to promote proliferation and matrix synthesis by wing chondrocytes in vitro. Together, our results suggest that the mechanism of action whereby IGFBP2 excess impairs long bone development is to inhibit IGF-mediated proliferation and matrix synthesis by the cartilage model; reduce the proliferation and progression to hypertrophy by the maturing chondrocytes; and attenuate proliferation and formation of the periosteal bony collar. These actions retard the growth and longitudinal expansion of the developing long bones, resulting in shortened wing skeletal elements. Our results emphasize the importance of a balance of IGF/IGFBP2 action at several stages during normal long bone development. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/16183342/Role_of_IGFBP2_IGF_I_and_IGF_II_in_regulating_long_bone_growth_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(05)00319-4 DB - PRIME DP - Unbound Medicine ER -