Growth Hormone and Insulin-Like Growth Factor I Induce Bone Morphogenetic Proteins 2 and 4: A Mediator Role in Bone and Tooth Formation?¹

Abstract

GH is known to increase the formation of bone and hard tissues of the tooth (dentine, cementum, and enamel), as do bone morphogenetic proteins. GH receptors are expressed in these tissues and could mediate local growth responses. Here we report that both GH and insulin-like growth factor I (IGF-I) are able to increase expression of bone morphogenetic protein-2 and -4 messenger RNAs 4- to 5-fold in human dental pulp fibroblasts in vitro. Induction was seen at physiological concentrations of hormone (25-100 ng/ml GH; 50-200 ng/ml IGF-I) and reached a maximum at 4-8 h. Immunoblot analysis demonstrated that the increase in messenger RNAs resulted in an increase in expressed protein. Anti-IGF-I inhibition experiments indicate that GH is able to induce the response without a requirement for local IGF-I production. These results raise the possibility that bone morphogenetic proteins mediate the local osteogenic actions of GH and IGF-I, and lend support to the view that GH can act through the mediation of factors other than IGF-I. These factors may combine with IGF-I in different tissues to enhance GH action and specificity.

Bone Morphogenetic Protein-4, a Novel Modulator of Melanogenesis

“…The BMP-4 effect on melanogenesis appears specific and is not the result of nonspecific cellular toxicity, as BMP-4 did not induce morphologic changes or melanocyte apoptosis; and was effective at doses widely used by other investigators (32)(33)(34). Using B16 mouse melanoma cells and melan-a, black non-agouti murine melanocytes, Martinez-Esparza et al (7,8) reported that TGF-␤1, a molecule that belongs to the superfamily of molecules that includes BMPs (9), decreased tyrosinase and TRP-1 levels (7) and activity (7,8).…”

A functional bone morphogenetic protein system in the ovary

“…It will be important to investigate the mechanisms that regulate BMP-4 and -7 expression in theca cells with respect to follicle fate. In this regard, it has been reported recently that growth hormone and insulin-like growth factor I (IGF-I) are potent stimulators of BMP-4 mRNA in human dental pulp fibroblasts cultured in vitro (30). It is also known that IGF-I is a potent stimulator of rat theca cell function (31,32) and that IGF-I expression is strong and weak in healthy and atretic follicles, respectively (33).…”

Cytokine regulation of syndecan‐1 and ‐2 gene expression in human periodontal fibroblasts and osteoblasts

“…Normal human PDLF, OB and GF were obtained from explant cultures of periodontal ligament, alveolar bone and gingiva, respectively, by using previously described methods (22). The cells were maintained in Dulbecco's modified Eagle's medium supplemented with 10% (v/v) heat inactivated fetal‐calf serum (FCS), 50 U/mL penicillin, 50 µg/mL streptomycin and 1% nonessential amino acids.…”