Regulatory role of osteogenic growth polypeptides in bone formation and hemopoiesis.

Osteogenic growth polypeptides such as the osteogenic growth peptide (OGP), fragments of the parathyroid hormone (PTH), and insulin-like growth factors (IGF) regulate bone cell activity in vitro and may affect in vivo osteoblastic functions in an autocrine, paracrine, or endocrine manner. Several growth polypeptides capable of regulating osteogenesis circulate in the blood in an inactive form, complexed to parent molecules or binding proteins. During postablation bone marrow regeneration these factors may be activated, released from the blood clot, and together with locally produced polypeptides mediate the initial intramedullary/systemic osteogenic phase of this process. Then osteogenic growth polypeptides expressed by osteoblasts and other stromal cells have the potential to promote the second phase of regeneration that consists of osteoclastogenesis, resorption of the transient intramedullary bone, and hemopoiesis. This is probably an indirect effect inasmuch as these polypeptides can regulate the stromal cell expression of hemopoietic factors such as macrophage colony stimulating factor (M-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6), and the stem cell factor (SCF). The postablation marrow regeneration model is suitable for studying the expression and activity of osteogenic growth polypeptides and already has been used to assess the effect of aging on these parameters. Clinically, the osteogenic growth polypeptides and marrow regeneration have a potential role in osteoporosis therapy, implant and corrective bone surgery, and bone marrow transplantation.