Authors:
Idris AI, Sophocleous A, Landao-Bassonga E, Canals M, Milligan G, Baker D, van’t Hof RJ, Ralston SH.
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.