Osteogenic growth peptide effects on primary human osteoblast cultures: Potential relevance for the treatment of glucocorticoid‐induced osteoporosis

Abstract The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide that has attracted considerable clinical interest as a bone anabolic agent and hematopoietic stimulator. In vivo studies on animals have demonstrated that the synthetic peptide OGP (10–14), reproducing the OGP C‐terminal active portion [H‐Tyr‐Gly‐Phe‐Gly‐Gly‐OH] increases bone formation, trabecular bone density and fracture healing. In vitro studies performed on cellular systems based on osteoblastic‐like cell lines or mouse stromal cells, have demonstrated that OGP (10–14) increases osteoblast proliferation, alkaline phosphatase (ALKP) activity and matrix synthesis and mineralization. In view of a potential application of OGP (10–14) in clinical therapy, we have tested different concentrations of OGP (10–14) on primary human osteoblast (hOB) cultures. We have observed significant increases of hOB proliferation (+35%), ALKP activity (+60%), osteocalcin secretion (+50%), and mineralized nodules formation (+49%). Our experimental model based on mature hOBs was used to investigate if OGP (10–14) could prevent the effects on bone loss induced by sustained glucocorticoid (GC) treatments. A strong decrease in bone formation has been attributed to the effects of GCs on osteoblastogenesis and osteocyte apoptosis, while an increase in bone resorption was due to a transient osteoblastic stimulation, mediated by the OPG/RANKL/RANK system, of osteoclasts recruitment and activation. Moreover, GCs act on hOBs decreasing the release of osteoprotegerin (OPG) a regulator of the RANKL/RANK interaction. Here, we provide evidences that OGP (10–14) inhibits hOB apoptosis induced by an excess of dexamethasone (−48% of apoptotic cells). Furthermore, we show that OGP (10–14) can increase OPG secretion (+20%) and can restore the altered expression of OPG induced by GCs to physiological levels. Our results support the employment of OGP (10–14) in clinical trials addressed to the treatment of different bone remodeling alterations including the GC‐induced osteoporosis. J. Cell. Biochem. 98: 1007–1020, 2006. © 2006 Wiley‐Liss, Inc.