title: Caffeine enhances osteoclast differentiation from bone marrow hematopoietic cells and reduces bone mineral density in growing rats.
abstract: Caffeine-containing beverage consumption has been associated with low bone mass and increased fracture risk in some, but not most, observational studies. The effects of caffeine on bone metabolism are still controversial. We investigated the effects of caffeine on the differentiation of bone progenitor cells and bone mineral density (BMD) by in vitro and in vivo experiments. Low-concentration caffeine (0.005-0.1 mM) did not affect the bone marrow cell viability and alkaline phosphatase activity during osteoblast differentiation from bone marrow stromal cells, but it effectively enhanced the osteoclastogenesis from bone marrow hematopoietic cells and the bone resorption activity by pit formation assay. Moreover, caffeine effectively enhanced the receptor activator of NF-κB ligand (RANKL), but reduced the osteoprotegerin protein expressions in osteoblast MC3T3-E1 cells. Caffeine could also increase the cyclooxygenase-2 (COX-2) protein expression and prostaglandin (PG)E(2) production in cultured neonatal mouse calvariae. In animal study, BMD in lumbar vertebra, femur, or tibia was significantly lowered in growing rats supplemented with 0.2% caffeine in diets for 20 weeks compared with the control group. The calcium contents in tibia and femur of caffeine-treated rats were also lower than that in the control group. The osteoclastogenesis of bone marrow cells isolated from caffeine-treated rats was markedly enhanced as compared with the control group. Taken together, these results suggest that caffeine may reduce BMD in growing rats through the enhancement in osteoclastogenesis. Caffeine may possess the ability to enhance a COX-2/PGE(2) -regulated RANKL-mediated osteoclastogenesis.
authors.affiliation: Institute of Toxicology, National Taiwan University, Taipei, Taiwan.
authors.forename: Shing Hwa
authors.initials: SH
authors.lastname: Liu
authors.forename: Chinliang
authors.initials: C
authors.lastname: Chen
authors.forename: Rong Sen
authors.initials: RS
authors.lastname: Yang
authors.forename: Yuan Peng
authors.initials: YP
authors.lastname: Yen
authors.forename: Ya Ting
authors.initials: YT
authors.lastname: Yang
authors.forename: Chingmin
authors.initials: C
authors.lastname: Tsai
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015519:Bone Density / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D002110:Caffeine / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine; D002118:Calcium