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

Aymen I Idris; Antonia Sophocleous; Euphemie Landao-Bassonga; Meritxell Canals; Graeme Milligan; David Baker; Robert J van't Hof; Stuart H Ralston

doi:10.1016/j.cmet.2009.07.006

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

Aymen I Idris, Antonia Sophocleous, Euphemie Landao-Bassonga, Meritxell Canals, Graeme Milligan, David Baker, Robert J van't Hof, Stuart H Ralston

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 PPARgamma. 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.

Original language	English
Pages (from-to)	139-147
Number of pages	9
Journal	Cell Metabolism
Volume	10
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2009.07.006
Publication status	Published - Aug 2009

Keywords / Materials (for Non-textual outputs)

Adipocytes
Animals
Bone Density
Cell Differentiation
Cells, Cultured
Cyclic AMP Response Element-Binding Protein
Female
Male
Mice
Mice, Knockout
Osteoblasts
Osteoporosis
PPAR gamma
Receptor, Cannabinoid, CB1
Stromal Cells

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10.1016/j.cmet.2009.07.006

http://www.sciencedirect.com/science/article/pii/S1550413109002022

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

abstract = "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 PPARgamma. 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.",

keywords = "Adipocytes, Animals, Bone Density, Cell Differentiation, Cells, Cultured, Cyclic AMP Response Element-Binding Protein, Female, Male, Mice, Mice, Knockout, Osteoblasts, Osteoporosis, PPAR gamma, Receptor, Cannabinoid, CB1, Stromal Cells",

author = "Idris, {Aymen I} and Antonia Sophocleous and Euphemie Landao-Bassonga and Meritxell Canals and Graeme Milligan and David Baker and {van't Hof}, {Robert J} and Ralston, {Stuart H}",

year = "2009",

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doi = "10.1016/j.cmet.2009.07.006",

language = "English",

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T1 - Cannabinoid Receptor Type 1 Protects against Age- Related Osteoporosis by Regulating Osteoblast and Adipocyte Differentiation in Marrow Stromal Cells

AU - Idris, Aymen I

AU - Sophocleous, Antonia

AU - Landao-Bassonga, Euphemie

AU - Canals, Meritxell

AU - Milligan, Graeme

AU - Baker, David

AU - van't Hof, Robert J

AU - Ralston, Stuart H

PY - 2009/8

Y1 - 2009/8

N2 - 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 PPARgamma. 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.

AB - 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 PPARgamma. 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.

KW - Adipocytes

KW - Animals

KW - Bone Density

KW - Cell Differentiation

KW - Cells, Cultured

KW - Cyclic AMP Response Element-Binding Protein

KW - Female

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Osteoblasts

KW - Osteoporosis

KW - PPAR gamma

KW - Receptor, Cannabinoid, CB1

KW - Stromal Cells

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U2 - 10.1016/j.cmet.2009.07.006

DO - 10.1016/j.cmet.2009.07.006

M3 - Article

C2 - 19656492

SN - 1550-4131

VL - 10

SP - 139

EP - 147

JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

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

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