Triiodothyronine (T3) stimulates insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-2 production by rat osteoblasts in vitro

Abstract

Osteoblast-like cells prepared from neonatal rat calvariae and grown under serum-free conditions produce IGF-1 and IGFBPs. In contrast to growth hormone, T3 and PTH increased both IGF-1 mRNA expression and net IGF-1 release in calvaria cells. In addition, they stimulated net production of IGFBP-3 and of an IGFBP with an apparent molecular weight of 32 kDa which was recognized by an antiserum against rat IGFBP-2. Bone cells expressed remarkably high levels of mRNA for IGFBP-2, the predominant IGFBP in serum of newborn rats. T3 at low physiological concentrations but not growth hormone stimulated IGFBP-2 mRNA expression and IGFBP-2 production in bone cells in vitro. Thus, IGFBPs are differentially regulated by these hormones and may play an autocrine/paracrine regulatory role in bone.

Interactions between GH, IGF-I, Glucocorticoids, and Thyroid Hormones during Skeletal Growth

“…IGFBP-4 is an inhibitor of cell proliferation, and this may be a mechanism that contributes to the antiproliferative effect of T3 in osteoblasts. T3 also stimulates IGF-I and IGFBP-2 expression in primary rat calvarial osteoblasts, whereas GH has no effect (114).…”

Thyroid hormone actions on cartilage and bone: interactions with other hormones at the epiphyseal plate and effects on linear growth

“…All these observations support the notion that bone is primarily responsive to T 3 , but that responsiveness is complex and may vary with development and vitamin D or retinoid status. In spite of this, no clearly documented transcriptionally activated T 3 target genes have yet been defined in bone cells, although interleukins-6 and -8 (Siddiqi et al 1996) and IGF binding proteins (IGFBPs)-2 (Schmid et al 1992) and-4 (Glantschnig et al 1996) have been implicated in preliminary studies in human, rat and murine species respectively. Findings of a recent study also suggest that IGF-I may be regulated directly by T 3 in rat vertebral, but not femoral, osteoblasts (Van Auken et al 1997).…”

“…In humans with hypothyroidism, there are reductions in GH-binding protein, IGF-I, IGF-II, IGFBP-3 and IGF bioactivity; these changes are reversed after thyroid hormone replacement (Miell et al 1993). Furthermore, in studies of cultured rat and mouse osteoblastic cells, it has been suggested that IGFBPs-2 (Schmid et al 1992) and -4…”

Mechanism of Thyroid Hormone-Induced Osteoporosis

“…IGF-I stimulates bone production by increasing osteoblast proliferation and matrix synthesis (21,22). T3 causes an increase in IGF-I production in UMR-106 osteoblastic cells and bone organ cultures (23,24). IGF-I mRNA in MC3T3-E1 osteoblastic cells is also increased after T3 treatment (25).…”