Contribution of marrow stromal cells to the regulation of osteoblast proliferation in rats: evidence for the involvement of insulin-like growth factors

Zhang, R.W.; Simmons, David J.; Crowther, Roger S.; Mohan, Subburaman; Baylink, David J.

doi:10.1016/0169-6009(91)90069-c

Cited by 34 publications

(11 citation statements)

References 42 publications

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“…It has been reported that osteoblasts synthesize IGF-I, -II, and IGFBPs, and gene expression is under the hormone control of numerous local and systemic factors [Schmid, 1995;Conover, 1996]. Marrow stromal cells also produce IGF-I, -II, and IGFBPs [Zhang et al, 1991;Schmid, 1995;Malpe et al, 1997;Rodan, 1998] and it is likely that stromal cells contribute substantially to the amount of IGFs and IGFBPs deposited in the skeletal matrix [Rosen et al, 1994]. It has been suggested that variations in the levels of expression of the IGF system components play a role in the differential regulation of bone metabolism at separate skeletal sites [Malpe et al, 1997].…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor binding proteins in femoral and vertebral bone marrow stromal cells: Expression and regulation by thyroid hormone and dexamethasone

et al. 2001

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Insulin-like growth factor (IGF)-I is an important regulator of bone metabolism. Clinical observations suggest that different anatomic sites within the adult skeleton respond differently to hormonal and therapeutic treatment, and recent studies on bone marrow stromal cells in culture show that there are skeletal site-dependent differences in the gene expression of IGF-I. The actions of IGF-I and -II on bone cells are known to be modulated by the IGF binding proteins (IGFBP)-1 through -6 and the Type I and Type II IGF receptors. Therefore, we compared the expression of IGFBP-1 through -6 in adult female rat bone marrow stromal cell cultures derived from two separate skeletal sites: vertebrae and femurs. The cultures were maintained simultaneously under conditions that support osteoblast differentiation from osteoprogenitors present in the femoral and vertebral marrow cell populations. We also addressed whether IGFBP messenger RNA levels are regulated by thyroid hormone (T(3)) and dexamethasone (dex) treatment in femoral vs. vertebral marrow stromal cells in vitro, since steroid hormones play an important role in skeletal function. Northern blot analyses revealed that there are distinct skeletal site differences in the gene expression of IGFBPs. The vertebral marrow cultures express IGFBP-2 through -6 mRNAs, with IGFBP-2, IGFBP-4, and IGFBP-6 mRNAs predominating. The femoral marrow stromal cell cultures express only IGFBP-4 and IGFBP-6. Importantly, vertebral marrow cultures have much higher IGFBP mRNA steady-state levels than femoral cultures for all the detected IGFBP transcripts. IGFBP-1 is not detected in either femoral or vertebral cultures. In addition to a skeletal site difference, we show that T(3) and dex regulate the expression of specific IGFBP mRNAs. T(3) treatment also upregulates IGF-I protein secretion by vertebral marrow stromal cell cultures. Interestingly, the type I receptor for IGF-I was expressed equivalently in cultures from the two skeletal sites. These findings have important implications for the anatomical site specificities of hormonal responses that are noted in the skeleton.

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Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor binding proteins in femoral and vertebral bone marrow stromal cells: Expression and regulation by thyroid hormone and dexamethasone

et al. 2001

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“…However, bone marrow stromal cells, which are rich sources of cytokines for hematopoietic progenitors, actively synthesize IGF-I and various IGFBPs (30,31). These cells mediate the actions of GH on granulocytic precursors through production of IGF-I.…”

Section: Bone and The Igfsmentioning

confidence: 99%

Insulin-like Growth Factors and Bone: The Osteoporosis Connection

Rosen

Donahue

Hunter

1994

Experimental Biology and Medicine

198

118

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In the last five years significant progress has been made defining the role of insulin-like growth factors (IGFs) in the process of bone remodeling. In this paper, we present critical evidence that IGF-I and IGF-II are produced by bone cells and regulate specific osteoblastic and osteoclastic functions. In addition, we review work from several laboratories establishing the role of the skeletal IGF binding proteins as an integral component of a unique IGF regulatory system. Data presented suggest that the calciotropic hormones active in the bone remodeling process may exert their effects through the IGF regulatory system. In contrast to the well-defined local action of IGF-I and IGF-II on the skeleton, the relationship between circulating IGF-I and bone remodeling is less certain. Newer data are presented which suggest the potential utility of serum growth factor measurements in certain clinical states. Finally, this paper presents an overview of the most current efforts to stimulate bone formation using recombinant IGFs. However, work on the beneficial aspects of IGFs for the skeleton remains preliminary at best with the eventual therapeutic role of IGF-I in osteoporosis yet to be defined.

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“…Bone cells synthesize IGF-I [4][5][6], which is probably an important local regulator of bone formation [7]. In vitro studies demonstrate that this polypeptide enhances the replication of preosteoblastic cells, stimulates the differentiated function of osteoblasts, and increases bone collagen synthesis and matrix apposition rates [8][9][10][11][12].…”

mentioning

confidence: 99%

Effect of estrogen deficiency on IGF-I plasma levels: Relationship with bone mineral density in perimenopausal women

et al. 1993

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Bone tissue is a source of growth factors; among them, insulinlike growth factor I (IGF-I) is probably an important local regulator of bone formation. This study has been carried out in order to assess the effects of natural menopause on plasma concentrations of IGF-I in the first 6 years after the cessation of gonadal function independent of age. We also examined the relationship between plasma IGF-I levels and bone mineral density (BMD) measured at the lumbar spine (LS), at the ultradistal radius (UDR), and at the junction of the distal and middle thirds of the radius (MR). Sixty-seven healthy nonobese women, aged 45-55, were studied (premenopausal n = 21; postmenopausal n = 46, from 1 to 6 years since menopause). Plasma IGF-I levels were measured by RIA, after acid-ethanol extraction. BMD of the forearm was measured by dual-photon densitometer and BMD of the LS was assessed by quantitative digital radiography. Mean values of IGF-I plasma levels were significantly reduced in postmenopausal women compared to the premenopausal group. Menopausal duration did not influence IGF-I plasma levels in postmenopausal women. We also found a positive correlation between IGF-I levels and BMD measured at MR both in pre- and postmenopausal women, while a correlation with LS and UDR-BMD was found only in fertile subjects. The results show that IGF-I plasma levels decrease immediately after menopause, since significantly lower levels are reached in the first years. The correlations found between plasma IGF-I levels and BMD suggest a possible role of reduced IGF-I in bone loss at particular skeletal sites.

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Contribution of marrow stromal cells to the regulation of osteoblast proliferation in rats: evidence for the involvement of insulin-like growth factors

Cited by 34 publications

References 42 publications

Insulin-like growth factor binding proteins in femoral and vertebral bone marrow stromal cells: Expression and regulation by thyroid hormone and dexamethasone

Insulin-like growth factor binding proteins in femoral and vertebral bone marrow stromal cells: Expression and regulation by thyroid hormone and dexamethasone

Insulin-like Growth Factors and Bone: The Osteoporosis Connection

Effect of estrogen deficiency on IGF-I plasma levels: Relationship with bone mineral density in perimenopausal women

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