Cannabinoid Receptor Type 1 Protects against Age-Related Osteoporosis by Regulating Osteoblast and Adipocyte Differentiation in Marrow Stromal Cells

被引：161

作者：

Idris, Aymen I. ^{[1
]}

Sophocleous, Antonia ^{[1
]}

Landao-Bassonga, Euphemie ^{[1
]}

Canals, Meritxell ^{[2
]}

Milligan, Graeme ^{[2
]}

Baker, David ^{[3
]}

van't Hof, Robert J. ^{[1
]}

Ralston, Stuart H. ^{[1
]}

机构：

[1] Univ Edinburgh, Inst Genet & Mol Med, Mol Med Ctr, Rheumat Dis Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Univ Glasgow, Fac Biomed & Life Sci, Mol Pharmacol Grp, Glasgow G12 8QQ, Lanark, Scotland

[3] Barts & London Queen Marys Sch Med & Dent, London E1 2AD, England

来源：

CELL METABOLISM | 2009年 / 10卷 / 02期

关键词：

BONE LOSS; ADIPOGENESIS; PHARMACOLOGY; EXPRESSION; CONVERSION; DENSITY; TISSUE; MASS;

D O I：

10.1016/j.cmet.2009.07.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Age-related osteoporosis is characterized by reduced bone formation and accumulation of fat in the bone marrow compartment. Here, we report that the type 1 cannabinoid receptor (CB1) regulates this process. Mice with CB1 deficiency (CB1(-/-)) had increased peak bone mass due to reduced bone resorption, but developed age-related osteoporosis with reduced bone formation and accumulation of adipocytes in the bone marrow space. Marrow stromal cells from CB1(-/-) mice had an enhanced capacity for adipocyte differentiation, a reduced capacity for osteoblast differentiation, and increased expression of phosphorylated CREB (pCREB) and PPAR gamma. Pharmacological blockade of CB1 receptors stimulated adipocyte differentiation, inhibited osteoblast differentiation, and increased cAMP and pCREB in osteoblast and adipocyte precursors. The CB1 receptor is therefore unique in that it regulates peak bone mass through an effect on osteoclast activity, but protects against age-related bone loss by regulating adipocyte and osteoblast differentiation of bone marrow stromal cells.

引用

页码：139 / 147

页数：9

共 32 条

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Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation [J].