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 (IGF)-I is an important regulator of bone metabo lism. Clinical observations suggest that different anatomic sites within th e 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. T he actions of ICF-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 re ceptors. Therefore, we compared the expression of IGFBP-1 through -6 in adu lt female rat bone marrow stromal cell cultures derived from two separate s keletal sites: vertebrae and femurs. The cultures were maintained simultane ously under conditions that support osteoblast differentiation from osteopr ogenitors present in the femoral and vertebral marrow cell populations. We also addressed whether ICFBP messenger RNA levels are regulated by thyroid hormone (T-3) and dexamethasone (dex) treatment in femoral vs, vertebral ma rrow stromal cells in vitro, since steroid hormones play an important role in skeletal function. Northern blot analyses revealed that there are distin ct skeletal site differences in the gene expression of IGFBPs. The vertebra l marrow cultures express IGFBP-2 through -6 mRNAs, with IGFBP-2, IGFBP-4, and IGFBP-6 mRNAs predominating. The femoral marrow stromal cell cultures e xpress only IGFBP-4 and IGFBP-6. Importantly, vertebral marrow cultures hav e much higher ICFBP mRNA steady-state levels than femoral cultures for all the detected ICFBP transcripts. IGFBP-1 is not detected in either femoral o r vertebral cultures. In addition to a skeletal site difference, we show th at T-3 and dex regulate the expression of specific ICFBP mRNAs. T-3 treatme nt also upregulates IGF-I protein secretion by vertebral marrow stromal cel l cultures. Interestingly, the type I receptor for IGF-I was expressed equi valently in cultures from the two skeletal sites. These findings have impor tant implications for the anatomical site specificities of hormonal respons es that are noted in the skeleton. (C) 2001 Wiley-Liss, Inc.