Osteogenic growth peptide is a potent anti-inflammatory and bone preserving hormone via cannabinoid receptor type 2

eLife

Moshe Neuman¹  Itai Bab¹  Natalya M Kogan¹  Malka Attar-Namdar¹  Bitya Raphael-Mizrahi²  Yankel Gabet²  Zvi Vogel³  Neta Rimmerman³  Arie Shteyer⁴  Mukesh Chourasia⁵  Joseph Tam⁵  Avital Shurki⁵  Roger G Pertwee⁶  Maria G Cascio⁶  Andreas Zimmer⁷ 

[1] Bone Laboratory, Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, Israel;Department of Anatomy & Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel;Department of Oral and Maxillofacial Surgery, Hadassah-Hebrew University Hospital, Jerusalem, Israel;Institute for Drug Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel;Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom;Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany;

关键词: osteogenic growth peptide;    endocannabinoid;    CB2;    cannabinoid receptor;    bone;    immunoregulation;   

DOI  :  10.7554/eLife.65834

来源: DOAJ

【 摘 要 】

The endocannabinoid system consists mainly of 2-arachidonoylglycerol and anandamide, as well as cannabinoid receptor type 1 and type 2 (CB2). Based on previous studies, we hypothesized that a circulating peptide previously identified as osteogenic growth peptide (OGP) maintains a bone-protective CB2 tone. We tested OGP activity in mouse models and cells, and in human osteoblasts. We show that the OGP effects on osteoblast proliferation, osteoclastogenesis, and macrophage inflammation in vitro, as well as rescue of ovariectomy-induced bone loss and prevention of ear edema in vivo are all abrogated by genetic or pharmacological ablation of CB2. We also demonstrate that OGP binds at CB2 and may act as both an agonist and positive allosteric modulator in the presence of other lipophilic agonists. In premenopausal women, OGP circulating levels significantly decline with age. In adult mice, exogenous administration of OGP completely prevented age-related bone loss. Our findings suggest that OGP attenuates age-related bone loss by maintaining a skeletal CB2 tone. Importantly, they also indicate the occurrence of an endogenous peptide that signals via CB2 receptor in health and disease.

【 授权许可】

Unknown