Caffeine regulates osteogenic differentiation and mineralization of primary adipose-derived stem cells and a bone marrow stromal cell line

• Published in: International journal of food sciences and nutrition Vol. 64; no. 4; pp. 429 - 436
• Main Authors: Su, Shu-Jem, Chang, Kee-Lung, Su, Shu-Hui, Yeh, Yao-Tsung, Shyu, Huey-Wen, Chen, Kuan-Ming
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.06.2013; Taylor & Francis; Taylor & Francis Ltd
• Subjects: Adipose Tissue - cytology; adipose-derived stem cell; Alkaline Phosphatase - metabolism; Animals; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - physiology; Bone density; Bone Density - drug effects; Bone Density - genetics; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - pharmacology; Bone marrow; bone marrow stromal cell; Caffeine; Caffeine - administration & dosage; Caffeine - pharmacology; Calcification, Physiologic - drug effects; Calcification, Physiologic - genetics; Cell Culture Techniques; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Line; Cells; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Food science; Genes; Hormesis; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - enzymology; Mesenchymal Stromal Cells - metabolism; Metabolism; Mice; Mice, Inbred C57BL; Osteoblasts - drug effects; Osteocalcin - genetics; Osteocalcin - metabolism; osteogenesis; Osteogenesis - drug effects; Osteogenesis - genetics; Osteoprotegerin - genetics; Osteoprotegerin - metabolism; Plant Extracts - pharmacology; Rats; Rats, Sprague-Dawley; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Stem Cells - drug effects; Stem Cells - enzymology; Stem Cells - metabolism; Up-Regulation; Weight
• ISSN: 0963-7486; 1465-3478
• DOI: 10.3109/09637486.2012.759184

Caffeine consumption reportedly influences bone mineral density and body weight. However, the effects of caffeine on bone metabolism are still controversial, and whether the dosage of caffeine influences osteogenic differentiation is yet to be clarified. In the present study, we cultured primary adipose-derived stem cells (ADSCs) and a bone marrow stromal cell line (M2-10B4) in osteogenic differentiation media containing varying concentrations of caffeine. Caffeine had biphasic effects: 0.1 mM caffeine significantly enhanced mineralization and alkaline phosphatase (ALP) activity. Consistent with these observations, a caffeine concentration of 0.1 mM upregulated the osteogenic differentiation marker genes ALP and osteocalcin (OCN), and elevated osteoprotegerin (OPG), Runt-related transcription factor 2 (RUNX2) and Sirtuin 1 (SIRT1) levels. However, a concentration of caffeine greater than 0.3 mM suppressed the differentiation of both the cell types. These findings indicate that caffeine has a beneficial effect on ADSCs and bone marrow stromal cells, enhancing differentiation to osteoblasts; this effect, which is mediated via RUNX2 activation at low doses is significantly suppressed at high doses.