Growth factors and the regulation of bone remodeling.

Canalis, Ernesto; McCarthy, Thomas L.; Centrella, Michael

doi:10.1172/jci113318

Cited by 576 publications

(219 citation statements)

References 35 publications

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“…Many types of polypeptide growth factor are present in the mineralized extracellular matrix of bone [2,3]. These growth regulatory factors include the insulinlike growth factors (IGFs, IGF-I and IGF-II), transforming growth factor ␤ (TGF␤), the fibroblast growth factors and the bone morphogenetic proteins.…”

Section: Growth Factors and Bone Remodellingmentioning

confidence: 99%

“…Recent experimental data indicate that local growth regulatory factors play a critical part in the control of the cellular events involved in bone formation [2], suggesting that these peptides could have a therapeutic role in osteoporosis. Numerous local growth factors have been isolated from conditioned mediums of cultured bone or from extracts of bone matrix, but we shall confine this review to the therapeutic potential of the most abundant growth factors in human bone [3], insulin-like…”

Section: Introductionmentioning

confidence: 99%

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The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective

Boonen¹,

Broos²,

Dequeker³

et al. 1997

Journal of Internal Medicine

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Boonen S, Broos P, Dequeker J, Bouillon R (Department of Internal Medicine, Division of Geriatric Medicine, the Arthritis and Metabolic Bone Disease Research Unit, the Department of Traumatology and Emergency Surgery and the Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium). The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective (Review). J Intern Med 1997; 242: 285–90. Both insulin‐like growth factor‐I (IGF‐I) and transforming growth factor β (TGFβ) have powerful modulatory effects in a variety of tissues. A major target of action is the skeletal system, where they enhance bone formation and decrease matrix degradation, thus playing a part in the maintenance of bone mass. Because of the potent mitogenic effect of these agents on osteoblasts, recombinant IGF‐I (rhIGF‐I) and recombinant TGFβ (rhTGFβ) have potential as drugs to stimulate bone formation in the prevention and treatment of osteoporosis. Using biochemical markers, subcutaneous rhIGF‐I therapy has been shown to increase bone turnover and bone formation in nonosteoporotic older people. However, a corresponding increase in bone mass has not yet been documented nor have there been reports yet on the effects of systemically administered rhTGFβ in humans. Further investigation is required to define the clinical potential of rhIGF‐I and rhTGFβ as therapeutic agents in age‐related osteoporosis.

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Section: Growth Factors and Bone Remodellingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective

Boonen¹,

Broos²,

Dequeker³

et al. 1997

Journal of Internal Medicine

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“…Understanding the modulation of the osteoblastic phenotype is of interest in light of the its important role in, for example, the formation of new bone during fracture healing as well as in the maintenance of existing bone to prevent osteoporosis [2]. Furthermore, carcinoma cells have an intriguing effect on the bone metabolism, including the formation of osteolytic and osteosclerotic metastases [36].…”

Section: K Iba Et Al/febs Letters 373 (1995) 1~1mentioning

confidence: 99%

“…Transforming growth factor fll (TGF-flj) is a multifunctional compound that affects the proliferation, differentiation and gene expression pattern of several cell types, including osteoblasts [1][2][3]. Bone is an abundant source of TGFofll [1,2] and in vivo studies have shown that TGF-fll is a local regulator of bone formation.…”

Section: Introductionmentioning

confidence: 99%

“…Bone is an abundant source of TGFofll [1,2] and in vivo studies have shown that TGF-fll is a local regulator of bone formation. In osteoblast cell culture systems, TGF-fll regulates the mineralization process and the expression of osteoblastic markers, including alkaline phosphatase, c~1 (I) procollagen, osteopontin, osteonectin and osteocalcin [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor‐β₁ downregulates dexamethasone‐indunced tetranectin gene expression during the in vitro mineralization of the human osteoblastic cell line SV‐HFO

et al. 1995

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In the present study, we examined the regulation of tetranectin gene expression using a human osteoblastic cell line, SV-HFO, that undergoes mineralization upon treatment with dexamethasone. We found that the expression of tetranectin and alkaline phosphatase mRNA was induced by dexamethasone treatment as evidenced by Northern blotting. When transforming growth factor-/] 1 (TGF-/] 0 was added together with dexamethasone to the SV-HFO cell cultures, the mineralization process was markedly suppressed and the expression of tetra nectin and alkaline phosphatase was downregulated in a dosedependent manner. These results demonstrate that the expression of tetranectin in these osteoblastic cells is regulated by dexamethasone and TGF-/] 1 and that tetranectin expression is tightly linked to the process of mineralization.of both alkaline phosphatase and osteocalcin [24]. More recently, we have shown that the cells undergo mineralization upon treatment with glucocorticoids [25]. In the present study, we used this human osteoblastic in vitro model system to begin analysing the regulation of tetranectin gene expression during mineralization. Tetranectin is a protein originally isolated from plasma [26] that was found to be expressed in bone at a time and space coincident with mineralization in vivo and in vitro [27]. We report that dexamethasone treatment induced the expression of tetranectin mRNA and that TGF-fl~ inhibited mineralization and the induction of tetranectin mRNA. Materials and methods

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Correlation of the osteoblastic phenotype with prostate-specific antigen expression in metastatic prostate cancer: implications for paracrine growth

et al. 1999

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The characteristic sclerotic appearance of bone metastases from prostate cancer is unexplained but could involve excess peritumoural activity of osteoblast mitogens such as the insulin‐like growth factors (IGFs). Since prostatic metastases are distinguished by androgen‐dependent secretion of prostate‐specific antigen (PSA), a serine protease which cleaves extracellular IGF‐binding proteins and thereby enhances the bioavailability of IGFs, the relationship was examined between tumour PSA expression and the osteoblastic phenotype. To this end, a cohort of 27 prostate cancer patients was evaluated to determine the relationship between serum PSA and radiographic bone lesion density at first presentation with metastatic disease. No linear correlation between absolute PSA levels and metastatic osteosclerosis was apparent. However, non‐parametric statistical analysis revealed a highly significant link between low‐PSA (<20 ng/ml) metastatic prostate cancer and osteolytic bone lesions (p < 0·0001, χ2 = 21·5). This finding raises the possibility that the osteoblastic phenotype of prostate cancer derives in part from PSA‐dependent proteolysis of IGF‐binding proteins within bone matrix. Copyright © 1999 John Wiley & Sons, Ltd.

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Growth factors and the regulation of bone remodeling.

Cited by 576 publications

References 35 publications

The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective

The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective

Transforming growth factor‐β₁ downregulates dexamethasone‐indunced tetranectin gene expression during the in vitro mineralization of the human osteoblastic cell line SV‐HFO

Correlation of the osteoblastic phenotype with prostate-specific antigen expression in metastatic prostate cancer: implications for paracrine growth

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Growth factors and the regulation of bone remodeling.

Cited by 576 publications

References 35 publications

The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective

The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective

Transforming growth factor‐β1 downregulates dexamethasone‐indunced tetranectin gene expression during the in vitro mineralization of the human osteoblastic cell line SV‐HFO

Correlation of the osteoblastic phenotype with prostate-specific antigen expression in metastatic prostate cancer: implications for paracrine growth

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Transforming growth factor‐β₁ downregulates dexamethasone‐indunced tetranectin gene expression during the in vitro mineralization of the human osteoblastic cell line SV‐HFO