Response of Bipotential Human Marrow Stromal Cells to Insulin-Like Growth Factors: Effect on Binding Protein Production, Proliferation, and Commitment to Osteoblasts and Adipocytes1

Abstract

Insulin-like growth factors (IGFs) are important regulators of the activity of mature osteoblasts, but their effects on osteoprogenitor cells in human bone marrow stroma are unclear. In this study, we assessed the effects of IGFs on a conditionally immortalized human marrow stromal cell line, hMS(3-4), which has the ability to differentiate to either mature osteoblasts or adipocytes. hMS(3-4) cells expressed functional receptors for IGFs as well as specific IGF-binding proteins (IGFBP-3, -4, -5, and -6). IGF treatment of hMS(3-4) cells did not alter IGFBP expression, but resulted in distinct posttranslational modifications of secreted IGFBP-3 and IGFBP-4 proteins. IGF-I, IGF-II, and their receptoractivating analogs significantly increased by 2-fold the proliferation rate of the hMS(3-4) cells, but had a more complex effect on hMS(3-4) cell differentiation. Treatment with IGFs did not affect gene expression of Cbfa1 or peroxisome proliferator-activated receptor ␥ 2 (transcription factors involved in commitment to osteoblast and adipocyte pathways, respectively), alkaline phosphatase, type I collagen, and osteocalcin (markers of the osteoblast lineage), or lipoprotein lipase and adipsin (markers of the adipocyte lineage) and did not change alkaline phosphatase activity or type I collagen and osteocalcin protein relative to total protein production. In contrast, IGFs significantly increased type I collagen expression in differentiated hMS(3-4) cells as well as mature osteoblasts and promoted lipid accumulation in differentiated adipocytes. In summary, hMS(3-4) cells express essential components of the IGF system and respond to IGF treatment with increased proliferation. There was no evidence for IGFs directly modulating the commitment of hMS(3-4) cells to either osteoblast or adipocyte pathways, and their effects on differentiation within these lineages were dependent on the stage of cell maturation. (Endocrinology 140: 5036 -5044, 1999)

The Role of Insulin-Like Growth Factor-2 on the Cellular Viability and Differentiation to the Osteogenic Lineage and Mineralization of Stem Cells Cultured on Deproteinized Bovine Bone Mineral

“…The various concentrations of IGF-2 were tested to evaluate/suggest the optimal concentration [16,25]. IGF-2 was used at different concentrations and concentrations ranging from 50 to 200 ng/mL promoted the proliferation of stem cells [16].…”

“…IGF-2 was used at different concentrations and concentrations ranging from 50 to 200 ng/mL promoted the proliferation of stem cells [16]. The application of IGF-2 at 200 ng/mL concentration enhanced the cellular proliferation of human marrow stromal cell line, which was shown by increased [ 3 H]thymidine incorporation and increase in the cell number [25]. In this study, the significant increase of osteogenesis and mRNA expression was seen both at 10 and 100 ng/mL, with the highest at 10 ng/mL concentration.…”