Histone H4-related osteogenic growth peptide (OGP): a novel circulating stimulator of osteoblastic activity.

Abstract

It has been established that regenerating marrow induces an osteogenic response in distant skeletal sites and that this activity is mediated by factors released into the circulation by the healing tissue. In the present study we have characterized one of these factors, a 14 amino acid peptide named osteogenic growth peptide (OGP). Synthetic OGP, identical in structure to the native molecule, stimulates the proliferation and alkaline phosphatase activity of osteoblastic cells in vitro and increases bone mass in rats when injected in vivo. Immunoreactive OGP in high abundance is present physiologically in the serum, mainly in the form of an OGP‐OGP binding protein complex. A marked increase in serum bound and unbound OGP accompanies the osteogenic phase of post‐ablation marrow regeneration and associated systemic osteogenic response. Authentic OGP is identical to the C‐terminus of histone H4 and shares a five residue motif with a T‐cell receptor beta‐chain V‐region and the Bacillus subtilis outB locus. Since these latter proteins have not been implicated previously in the control of cell proliferation or differentiation, OGP may belong to a novel, heretofore unrecognized family of regulatory peptides. Perhaps more importantly, OGP appears to represent a new class of molecules involved in the systemic control of osteoblast proliferation and differentiation.

Biosynthesis of Osteogenic Growth Peptide via Alternative Translational Initiation at AUG85 of Histone H4 mRNA

“…1C). OGP is present in micromolar concentrations in the serum of mammals, including humans (8,9), and is secreted by cultured cells such as NIH3T3 fibroblasts, MC3T3-E1 osteoblastic cells (10), and ROS 17/2.8 osteosarcoma cells (Fig. 1A).…”

“…In cell culture models, OGP regulates cell proliferation and activity (8,11). In in vivo rodent models, OGP increases bone mass (8), stimulates blood and bone marrow cellularity, and enhances engraftment of bone marrow transplants (12). The amino acid sequence identity between OGP and the carboxyl-terminal region of histone H4 prompted us to test the hypothesis that OGP is derived from histone H4 gene (s).…”

Resposta osteogênica sistêmica no estímulo medular ósseo

“…Some authors have been conducting experiments in an attempt to isolate substances produced on bodies, which would supposedly be correlated to bone formation. [8][9][10][11][12][13][14]22 In this experiment, three groups of animals were used: group A, submitted to ostectomy and to bone marrow remote stimulation by ablation, in order to assess the systemic osteogenic response after an intensive bone marrow regeneration process; group B, submitted to ostectomy and to bone marrow remote stimulation by placing a Kirschner wire inside the bone marrow in order to assess the systemic osteogenic response after an intensive bone marrow regeneration process , and; group C -control group -which was used for comparison. On the three groups, we performed blood depletion and used a garrote on the operated limb with an elastic band in order to reduce bleeding.…”

“…The synthetic OGP with an identical structure as the original one has stimulated the proliferation and activation of alkaline phosphatase of in vitro osteoblastic cells and has increased bone mass in rats. [11][12][13][14] Blood leakage is also directly correlated to the stimulation and activation of bone marrow. The production of erythropoietic cells may be associated to the production of osteogenic cells, by the correlation of its stem cells or by the release of factors affecting the differentiation and proliferation of stromal cell components of bone marow.…”

Osteogenic actions of the osteogenic growth peptide on bovine marrow mesenchymal stromal cells in culture

“…Also, during osteogenesis induced by DEX, bovine MSC could form calcificated nodules and express BGP mRNA. In in vivo rodent models, OGP enhances bone formation by increasing trabecular bone mass (Bab et al, 1992). Moreover, it induces a balanced increase in whole blood cell counts and overall bone marrow cells, and improves engraftment of bone marrow transplants (Gurevitch et al, 1996).…”