Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells

Abstract

Previous studies have shown that the actions of IGF-II in bone are determined not only by its concentration, but also by the concentration of IGFBP-4 as well as other IGFBPs. In this study, we sought to determine by Western ligand blotting the effects of growth hormone, IGF-I and IGF-II on the production of IGFBP-3 and IGFBP-4 in TE89 human osteosarcoma cells and in untransformed normal human bone cells derived from rib. Human growth hormone at 10 μg/l decreased the amount of IGFBP-4 but had no effect on the IGFBP-3 level in the conditioned medium of low density cultures of TE89 cells and human bone cells derived from rib. Human growth hormone had no effect on IGFBP-3 or IGFBP-4 levels in the conditioned medium of high density human bone cell cultures. IGF-I and IGF-II, which increased human bone cell proliferation, decreased the level of IGFBP-4 (30% of control at 100 μg/l IGF-I and IGF-II) but increased the level of IGFBP-3 (3–10 fold at 100 μg/l IGF-I and IGF-II) after 48 h of treatment in the conditioned medium of both low and high density TE89 cell cultures. Similar changes in IGFBP-3 and IGFBP-4 levels were also seen in the conditioned medium of human bone cells derived from rib after treatment with IGF-I and IGF-II. Studies to determine the underlying molecular mechanisms by which IGF-II decreased the amount of IGFBP-4 in the conditioned medium revealed that IGF-II decreased the IGFBP-4 mRNA abundance and increased the IGFBP-3 mRNA abundance in human bone cells. Based on the above findings, we conclude that the production of both IGFBP-3 and IGFBP-4 is regulated in bone cells and that local and systemic agents may modulate the responsiveness of bone cells to IGFs by regulated secretion of IGFBP-3 and IGFBP-4.

Cissus quadrangularis augments IGF system components in human osteoblast like SaOS-2 cells

“…In the current study, the increase in IGFBP 3 protein may be due to a decrease in degradation of the protein. IGFs are reported to protect IGFBP 3 from proteolysis [54] and to increase the secretion of IGFBP-3 by TE89 human osteosarcoma cells [36]. Thus, the increase in IGFs could have decreased the IGFBP 3 proteolysis as evinced by increased IGFBP 3 in the conditioned media after C. quadrangularis treatment.…”

Protein intake, calcium balance and health consequences

“…IGF-1 is a major regulator of bone metabolism that can act as a systemic and local regulator of osteoblastic function (Mohan et al, 1992;Langdahl et al, 1998) and as a coupling factor in bone remodeling by activating both bone resorption and bone formation (Rubin et al, 2002). As reviewed by Bonjour et al (1997) and Thissen et al (1994), the impact of dietary protein on IGF-1 and the impact, in turn, of IGF-1 on bone health has a key role in the prevention of osteoporosis.…”

Serum Levels of Insulin-like Growth Factor Binding Proteins (IGFBP)–4 and –5 Correlate with Bone Mineral Density in Growth Hormone (GH)–Deficient Adults and Increase with GH Replacement Therapy

“…(1) Based on the findings that exogenous addition of GH to bone cells in serum-free culture stimulates proliferation, (10,11) and that bone cells contain GH receptors, (12) it has been proposed that GH may mediate some of its effects directly via GH receptors in the target cells. Based on the findings that GH treatment increases both systemic and local production of insulin-like growth factor (IGF)-I, (13,14) and that IGF-I has important effects on skeletal metabolism, (15) it has also been proposed that GH may mediate its effects indirectly via modulating the endocrine as well as local actions of IGF.…”