Osteoprotective Roles of Green Tea Catechins

Abstract

Osteoporosis is the second most common disease only secondary to cardiovascular disease, with the risk of fracture increasing with age. Osteoporosis is caused by an imbalance between osteoblastogenesis and osteoclastogenesis processes. Osteoclastogenesis may be enhanced, osteoblastogenesis may be reduced, or both may be evident. Inflammation and high reactive oxygen enhance osteoclastogenesis while reducing osteoblastogenesis by inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation. Catechins, the main polyphenols found in green tea with potent anti-oxidant and anti-inflammatory properties, can counteract the deleterious effects of the imbalance of osteoblastogenesis and osteoclastogenesis caused by osteoporosis. Green tea catechins can attenuate osteoclastogenesis by enhancing apoptosis of osteoclasts, hampering osteoclastogenesis, and prohibiting bone resorption in vitro. Catechin effects can be directly exerted on pre-osteoclasts/osteoclasts or indirectly exerted via the modulation of mesenchymal stem cells (MSCs)/stromal cell regulation of pre-osteoclasts through activation of the nuclear factor kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Catechins also can enhance osteoblastogenesis by enhancing osteogenic differentiation of MSCs and increasing osteoblastic survival, proliferation, differentiation, and mineralization. The in vitro effects of catechins on osteogenesis have been confirmed in several animal models, as well as in epidemiological observational studies on human subjects. Even though randomized control trials have not shown that catechins provide anti-fracture efficacy, safety data in the trials are promising. A large-scale, placebo-controlled, long-term randomized trial with a tea regimen intervention of optimal duration is required to determine anti-fracture efficacy.

Keywords: antioxidant; apoptosis; green tea extract; inflammation; mesenchymal stem cells; osteoprotection.

Figure 1

Summarized mechanisms of green tea polyphenols (GTP) in bone protection. Green tea catechins increase antioxidant capacities, reduce oxidative stress, and suppress the production of pro-inflammatory mediators. In osteoblasts, GTP inhibits oxidative stress by the upregulation of Runx2, Wnt, TGF-β, Osterix, Osteocalcin, and ALP. Moreover, RANKL, TRAP, and NF-κB activities are downregulated and caspase- 3 and Fenton reaction activities are upregulated in osteoclasts by GTP treatment. These actions should contribute to enhance bone formation/mineralization, and reduce bone resorption/erosion, resulting in increased bone mass, bone mineral density, and bone strength, leading to a reduced risk of bone fracture. ALP, alkaline phosphatase; GPX, glutathione peroxidase; NF-κB, nuclear transcription factor-κB; PGE2, prostaglandin E2; RANKL, receptor activator of nuclear transcription factor-κB ligand; Runx2, Runt-related transcription factor 2; SOD, superoxide dismutase; TGF-β, transforming growth factor β; TRAP, tartrate-resistant acid phosphatase; ↑, upregulated; ↓, downregulated.