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

Abstract

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.

Effects of Coffee Intake and Intraperitoneal Caffeine on Bone Repair Process - A Histologic and Histometric Study

“…Possibly in CAF group there was greater plasma concentration of caffeine compared to the CO group, consequently higher bioavailability during the healing process after tooth extraction. This increased supply in the repair site possibly led to changes in intracellular mediators and thus to a lower viability and activity of osteoblasts to synthesize bone matrix, as evidenced in several studies (8,20,21), and also higher osteoclastic activity (19), which may have provided low maturity of bone trabeculae with the use of pure caffeine (Figs. 1F, I).…”

“…The indirect actions may occur secondarily to changes in mineral bone homeostasis (calcium and phosphorus), or through changes in hormones or absorption and excretion regulators of these minerals (6,18). Evidence for direct actions of caffeine in the metabolism of bone cells was mainly obtained in studies of cell culture, showing changes in both osteoblasts and osteoclasts (19,20).…”

“…The quality evaluation of bone repair process in the dental socket of animals treated with coffee or caffeine revealed that the newly formed bone trabeculae did not have suitable maturity even on 21 st Many studies have demonstrated that caffeine acts directly on osteoblasts and osteocytes disturbing the process of differentiation (20) multiplication (9), bone matrix production and mineralization (20), even leading to apoptosis of these cells (21). In osteoclasts, it is suggested that the presence of caffeine may increase the differentiation of these cells with the consequent decrease of bone mineral density (19).…”

Caffeine alters the effects of bone marrow-derived mesenchymal stem cells on neutrophils

“…1,2 Caffeine possesses various effects on different body systems, including endocrine, cardiovascular, respiratory, urinary, gastrointestinal metabolism, immunity, and especially the central nervous system. 3,4 In fact, caffeine is the world's most widely and legally consumed psychoactive drug. 3 Caffeine is structurally similar to adenosine.…”

“…3,4 In fact, caffeine is the world's most widely and legally consumed psychoactive drug. 3 Caffeine is structurally similar to adenosine. Indeed, it is capable of binding to adenosine receptors without activating them, suggesting that caffeine is a competitive inhibitor of adenosine.…”