Osteogenic growth peptide
A 14-residue blood peptide that matches the end of histone H4, builds bone in rodents and acts on the cannabinoid CB2 receptor, but has never been given to people
Osteogenic growth peptide (OGP) was found in 1992 in the blood of rats whose bone marrow was regenerating. It is identical to the last 14 amino acids of histone H4, the protein that packages DNA, and cells make it by starting to read the histone message part-way along. In rats, rabbits and mice it increased bone mass, sped some fractures, boosted blood-cell recovery after marrow transplant and, in recent work, acted on the cannabinoid CB2 receptor against bone loss, inflammation and lung scarring. People carry it in their serum too. It has never been tested as a treatment in humans and is not approved anywhere.
No established human dose Details ↓
Recommended Dosing
No established human dose
Osteogenic growth peptide has never been given to a person. The single human study measured the peptide already present in normal serum, and a 2022 paper added that serum levels fall with age in premenopausal women.
What is it?
When bone marrow is damaged and regrows, bone elsewhere in the skeleton thickens, which suggested that healing marrow sends a signal through the blood. In 1992 an Israeli group isolated one such signal, a 14-amino-acid peptide they named osteogenic growth peptide. Synthetic OGP made bone-forming cells divide and raise alkaline phosphatase, increased bone mass when injected into rats, and rose in serum during marrow regeneration. To the authors' surprise it was identical to the last 14 residues of histone H4. Later work showed that cells produce it by starting translation at an internal start codon of the histone H4 message, so one gene yields both a DNA-packaging protein and a secreted peptide.
OGP is plentiful in blood. A 1995 study purified it from normal human serum, found it identical in sequence and activity to the rat and mouse peptide, and measured total immunoreactive OGP at levels far above those of most hormones, at least 80% of it bound to a carrier. Alpha-2-macroglobulin was later identified as one human binding protein, and its native form increased OGP's effect on bone cells in culture. In animals, injected OGP sped fracture healing in rabbits under unstable fixation, enlarged and organised fracture callus in rats, increased white cells and marrow cellularity in mice, and doubled survival after irradiation and marrow transplant.
A 2022 study reframed OGP as a hormone of the endocannabinoid system. Its effects on bone cells, bone-resorbing cells and inflammatory macrophages disappeared when the cannabinoid CB2 receptor was removed or blocked; it bound CB2; and in mice it prevented bone loss after ovary removal and with ageing. Its circulating levels fell with age in premenopausal women. The same group has since reported that OGP reduced intestinal tumours in a mouse cancer model and lung scarring in young and old mice.
Almost everything known about OGP comes from cells and animals. The one study of OGP in people measured it in serum; no study has given OGP to a human being, so there is no human dose and no human safety record. Much of the recent literature uses OGP or its five-residue fragment as a coating or payload in bone-repair scaffolds and implants, which is engineering research rather than evidence about the peptide as a drug. This entry is kept at mid depth for that reason: the human evidence is a single measurement study.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Mechanism of Action
OGP is a fragment translated from the histone H4 message and secreted into the blood, where carrier proteins hold most of it.
From the histone H4 gene
Made by translation starting inside the histone H4 message, then trimmed to 14 residues and secreted (PMID 10318873).
Bone and marrow cells
Stimulates osteoblast and marrow stromal cell growth and bone formation in rodents (PMIDs 1582415, 12228919).
CB2 receptor
Binds the cannabinoid CB2 receptor, through which it limited bone loss and inflammation in mice (PMID 35604006).
Published Research
Studies of osteogenic growth peptide itself, read from their PubMed abstracts: the discovery, its origin from histone H4, its binding protein, the one human serum study, animal studies of bone, fracture, blood formation, cancer and fibrosis, and two reviews. Studies of the shorter fragment OGP(10-14), a different molecule, and of scaffolds carrying OGP are not carded.
Found in human serum
Normal human serum contained OGP and its binding protein. Total immunoreactive OGP ranged from 480 to 4,460 micromol/L, at least 80-90% of it bound, and the free-to-total ratio declined between ages 23 and 49. The purified human peptide matched rat and mouse OGP in sequence, immunoreactivity and ability to make cells divide.
Discovery in regenerating marrow
A 14-residue peptide released during marrow regeneration stimulated the growth and alkaline phosphatase activity of bone-forming cells and increased bone mass when injected into rats. Serum OGP, mostly bound to a carrier, rose during the bone-forming phase after marrow ablation, and the peptide matched the C-terminus of histone H4.
Made from the histone H4 message
OGP messenger RNA could not be told apart from histone H4 messenger RNA, and cells given a modified H4 gene secreted the matching modified OGP. Translation began at an internal start codon (AUG85) through leaky ribosomal scanning, producing a precursor that was cut to OGP.
Alpha-2-macroglobulin binds it
OGP bound native and activated human plasma alpha-2-macroglobulin, and OGP was purified from a commercial preparation of the protein. In mouse bone cells, small amounts of native alpha-2-macroglobulin increased OGP's growth effect, while the activated form blocked it, suggesting roles in delivering and clearing the peptide.
Acts through the CB2 receptor
OGP's effects on osteoblast growth, osteoclast formation and macrophage inflammation, its rescue of bone loss after ovary removal and its prevention of ear swelling were all lost without the cannabinoid CB2 receptor. OGP bound CB2, prevented age-related bone loss in adult mice, and its blood levels fell with age in premenopausal women.
Faster fracture healing in rabbits
Rabbits with tibial fractures were given OGP intravenously from day four. Under unstable plate fixation, bone covered the callus cartilage by day seven instead of ten and the cortex united by 21-28 days; callus size did not change, and fractures under stable compression plates healed no faster.
Fracture callus in rats
Rats with femoral fractures received 25 ng of OGP under the skin daily for a week. Marrow cells from the opposite femur became more proliferative and bone-forming, TGF-beta and other growth-factor genes rose, and callus was larger and organised earlier, though the histological comparisons did not reach significance.
Blood formation and marrow transplant
In normal mice OGP raised white cell counts and marrow cellularity in a balanced way. In mice given lethal irradiation and a marrow transplant, OGP started before irradiation sped blood-cell recovery and doubled survival, without favouring the recipient's own residual cells.
Fewer intestinal tumours in mice
Weekly OGP injections in a mouse model prone to intestinal adenomas reduced tumour number and size, lowered IL-6 and IL-4, increased anti-tumour CD8 T cells and reduced tumour-promoting myeloid cells. A UK Biobank analysis linked a common CB2 receptor variant with monocyte counts in people, which concerns the receptor, not OGP.
Less lung scarring in mice
In young and aged mice with bleomycin-induced lung fibrosis, daily OGP injections improved survival, reduced weight loss, collagen and fibrosis scores, and outperformed hydrocortisone. Immune cell counts were unchanged, and OGP slowed the growth of myofibroblasts in culture.
From concept to drug design
This review summarises OGP and its fragment OGP(10-14) as micromolar serum peptides that increase bone formation and fracture healing in rodents, regulate bone-marrow stromal cells, enhance blood formation after marrow transplant and chemotherapy, and depend on tyrosine-10 and phenylalanine-12 for activity.
Role in bone regeneration
This review describes the chemistry of OGP and OGP(10-14), the pathways thought to drive osteoblast growth and differentiation, which remain incompletely understood, and their wide use in bone tissue engineering.
Side Effects & Contraindications
Reported Side Effects
OGP has never been given to people, so no human side effects are known.
Contraindications & Cautions
OGP is not an approved medicine anywhere.
Legal Status
Osteogenic growth peptide is a research peptide, not a medicine.
Frequently Asked Questions
?What is osteogenic growth peptide?
A 14-amino-acid peptide found in blood that matches the last 14 residues of histone H4. It stimulates bone-forming cells and increased bone mass in rodents.
?Has it been tested in people?
Only measured. A 1995 study found it in normal human serum, and a 2022 study reported that levels fall with age in premenopausal women. No study has given it to a person.
?Is OGP the same as OGP(10-14)?
No. OGP(10-14) is its last five residues, YGFGG, a separate molecule with its own studies. This page covers the full 14-residue peptide.
?What does CB2 have to do with it?
A 2022 study found that OGP binds the cannabinoid CB2 receptor and that its bone-protective and anti-inflammatory effects in mice needed that receptor.
?Can it be used for fractures or osteoporosis?
Not outside research. It sped some fractures in rabbits and prevented bone loss in mice, but it is not approved, has no human dose and has never been tested for safety in people.
References
- [pubmed] Greenberg Z, et al. "Structural and functional characterization of osteogenic growth peptide from human serum: identity with rat and mouse homologs." J Clin Endocrinol Metab, 1995;80(8):2330-5. PMID: 7629225.
- [pubmed] Bab I, et al. "Histone H4-related osteogenic growth peptide (OGP): a novel circulating stimulator of osteoblastic activity." EMBO J, 1992;11(5):1867-73. PMID: 1582415.
- [pubmed] Bab I, et al. "Biosynthesis of osteogenic growth peptide via alternative translational initiation at AUG85 of histone H4 mRNA." J Biol Chem, 1999;274(20):14474-81. PMID: 10318873.
- [pubmed] Gavish H, et al. "Human alpha 2-macroglobulin is an osteogenic growth peptide-binding protein." Biochemistry, 1997;36(48):14883-8. PMID: 9398211.
- [pubmed] Raphael-Mizrahi B, et al. "Osteogenic growth peptide is a potent anti-inflammatory and bone preserving hormone via cannabinoid receptor type 2." Elife, 2022;11. PMID: 35604006.
- [pubmed] Sun YQ, et al. "Osteogenic growth peptide enhances the rate of fracture healing in rabbits." Cell Biol Int, 1998;22(4):313-9. PMID: 10101048.
- [pubmed] Brager MA, et al. "Osteogenic growth peptide normally stimulated by blood loss and marrow ablation has local and systemic effects on fracture healing in rats." J Orthop Res, 2000;18(1):133-9. PMID: 10716289.
- [pubmed] Gurevitch O, et al. "Osteogenic growth peptide increases blood and bone marrow cellularity and enhances engraftment of bone marrow transplants in mice." Blood, 1996;88(12):4719-24. PMID: 8977266.
- [pubmed] Iden JA, et al. "Immunomodulatory function of cannabinoid receptor 2 and its agonist osteogenic growth peptide in health and cancer: a study in mice and humans." Oncogene, 2025;44(29):2504-2514. PMID: 40307509.
- [pubmed] Younis L, et al. "Therapeutic potential of cannabinoid receptor 2 agonist osteogenic growth peptide in lung fibrosis in aged mice." Am J Respir Cell Mol Biol, 2026;74(7):965-968. PMID: 42089318.
- [review] Bab I, et al. "Osteogenic growth peptide: from concept to drug design." Biopolymers, 2002;66(1):33-48. PMID: 12228919.
- [review] Pigossi SC, et al. "Role of Osteogenic Growth Peptide (OGP) and OGP(10-14) in Bone Regeneration: A Review." Int J Mol Sci, 2016;17(11). PMID: 27879684.
- [other] PubChem CID 25079049, Osteogenic growth peptide: formula C68H110N22O18, molecular weight 1523.7. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/25079049
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Formula and weight from PubChem; status from Drugs@FDA (openFDA) and the EMA medicines list. Grey Peptides sells nothing and links to no vendor.
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