Osteoporosis is the second most-prevalent epidemiologic disease in the aging population worldwide. Cross-sectional and retrospective evidence indicates that tea consumption can mitigate bone loss and reduce risk of osteoporotic fractures. Tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis in vitro. Previously, we showed that (−)-epigallocatechin-3-gallate (EGCG), one of the green tea polyphenols, increased osteogenic differentiation of murine bone marrow mesenchymal stem cells (BMSCs) by increasing the mRNA expression of osteogenesis-related genes, alkaline phosphatase activity and, eventually, mineralization. We also found that EGCG could mitigate bone loss and improve bone microarchitecture in ovariectomy-induced osteopenic rats, as well as enhancing bone defect healing partially via bone morphogenetic protein 2 (BMP2). The present study investigated the effects of EGCG in human BMSCs. We found that EGCG, at concentrations of both 1 and 10 µmol/L, can increase mRNA expression of BMP2, Runx2, alkaline phosphatase (ALP), osteonectin and osteocalcin 48 h after treatment. EGCG increased ALP activity both 7 and 14 days after treatment. Furthermore, EGCG can also enhance mineralization two weeks after treatment. EGCG without antioxidants also can enhance mineralization. In conclusion, EGCG can increase mRNA expression of BMP2 and subsequent osteogenic-related genes including Runx2, ALP, osteonectin and osteocalcin. EGCG further increased ALP activity and mineralization. Loss of antioxidant activity can still enhance mineralization of human BMSCs (hBMSCs).

Osteoporosis is the second most common epidemiologic disease in the aging population worldwide. Previous studies have found that frequent tea drinkers have higher bone mineral density and less hip fracture. We previously found that (−)-epigallocatechin gallate (EGCG) (20–100 µmol/L) significantly suppressed receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis and pit formation via inhibiting NF-κB transcriptional activity and nuclear transport of NF-κB in RAW 264.7 cells and murine primary bone marrow macrophage cells. The most important regulation in osteoclastogenesis is the receptor activator of nuclear factor-kB/RANKL/osteoprotegrin (RANK/RANKL/OPG) pathway. In this study, we used the coculture of RAW 264.7 cells and the feeder cells, ST2, to evaluate how EGCG regulated the RANK/RANKL/OPG pathway in RAW 264.7 cells and ST2 cells. We found EGCG decreased the RANKL/OPG ratio in both mRNA expression and secretory protein levels and eventually decreased osteoclastogenesis by TRAP (+) stain osteoclasts and TRAP activity at low concentrations—1 and 10 µmol/L—via the RANK/RANKL/OPG pathway. The effective concentration can be easily achieved in daily tea consumption. Taken together, our results implicate that EGCG could be an important nutrient in modulating bone resorption.

Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance the osteogenic differentiation of murine bone marrow mesenchymal stem cells and inhibit the osteoclastogenesis in RAW264.7 cells by modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) (RANK/RANKL/OPG) pathway. Our previous study also found that EGCG can promote bone defect healing in the distal femur partially via bone morphogenetic protein-2 (BMP-2). Considering the osteoinduction property of BMP-2, we hypothesized that EGCG could accelerate the bone healing process with an increased expression of BMP-2. In this manuscript, we studied whether the local use of EGCG can facilitate tibial fracture healing. Fifty-six 4-month-old rats were randomly assigned to two groups after being weight-matched: a control group with vehicle treatment (Ctrl) and a study group with 10 µmol/L, 40 µL, EGCG treatment (EGCG). Two days after the operation, the rats were treated daily with EGCG or vehicle by percutaneous local injection for 2 weeks. The application of EGCG enhanced callus formation by increasing the bone volume and subsequently improved the mechanical properties of the tibial bone, including the maximal load, break load, stiffness, and Young’s modulus. The results of the histology and BMP-2 immunohistochemistry staining showed that EGCG treatment accelerated the bone matrix formation and produced a stronger expression of BMP-2. Taken together, this study for the first time demonstrated that local treatment of EGCG can accelerate the fracture healing process at least partly via BMP-2.

(-)-Epigallocatechin 3-gallate (EGCG) is the main active green tea catechin and has a wide variety of benefits for health. Post-traumatic osteoarthritis (PTOA) occurs as a consequence of joint injuries that commonly happen in the young population. In this study, we investigated the effects of EGCG on PTOA prevention by using the anterior cruciate ligament transection (ACLT)–OA model and further investigated the roles of autophagy in OA treatment. Our results showed that intra-articular injection of EGCG significantly improved the functional performances and decreased cartilage degradation. EGCG treatment attenuated the inflammation on synovial tissue and cartilage through less immunostained cyclooxygenase-2 and matrix metalloproteinase-13. We further noted EGCG may modulate the chondrocyte apoptosis by activation of the cytoprotective autophagy through reducing the expression of the mTOR and enhancing the expression of microtubule-associated protein light chain 3, beclin-1, and p62. In conclusion, intra-articular injection of EGCG after ACL injury inhibited the joint inflammation and cartilage degradation, thereby increasing joint function. EGCG treatment also reduced the chondrocyte apoptosis, possibly by activating autophagy. These findings suggested that EGCG may be a potential disease-modifying drug for preventing OA progression.

Osteoarthritis (OA) is the most prevalent joint disease that causes an enormous burden of disease worldwide. (−)-Epigallocatechin 3-gallate (EGCG) has been reported to reduce post-traumatic OA progression through its anti-inflammatory property. Aging is the most crucial risk factor of OA, and the majority of OA incidences are related to age and not trauma. In this study, we assess whether EGCG can ameliorate cartilage degradation in primary OA. In an in-vitro study, real-time PCR was performed to assess the expression of genes associated with human articular chondrocyte homeostasis. A spontaneously occurring OA model in guinea pigs was used to investigate the effect of EGCG in vivo. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical (IHC) analysis to determine the protein level of type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), and p16 ^ink4a in articular cartilage. In the in-vitro study, EGCG increased the gene expression of aggrecan and Col II and decreased the expression of interleukin-1, cyclooxygenase 2, MMP-13, alkaline phosphatase, Col X, and p16 ^Ink4a; EGCG treatment also attenuated the degraded cartilage with a lower OARSI score. Meanwhile, IHC results showed that EGCG exerted an anti-OA effect by reducing ECM degradation, cartilage inflammation, and cell senescence with a less-immunostained Col II, MMP-13, and p16 ^Ink4a. In conclusion, these findings suggest that EGCG may be a potential disease-modifying OA drug for the treatment of primary OA.

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is the most common cause of mortality and neurological disability in infancy after perinatal asphyxia. Reliable biomarkers to predict neurological outcomes of neonates after perinatal asphyxia are still not accessible in clinical practice. Methods: A prospective cohort study enrolled neonates with perinatal asphyxia. Biochemical blood tests and cerebral Doppler ultrasound were measured within 6 h of age and at the 4th day old. Neurological outcomes were assessed at 1 year old. Results: Sixty-four neonates with perinatal asphyxia were enrolled. Fifty-eight (90%) had hypoxic-ischemic encephalopathy (HIE) including 20 (34%) Stage I, 21 (36%) Stage II, and 17 (29%) Stage III. In the asphyxiated infants without therapeutic hypothermia, HIE stage, PH, and base excess levels within 6 h of age were the predictors of adverse outcomes. In the asphyxiated infants receiving therapeutic hypothermia, HIE stage failed to predict outcomes. Instead, blood lactate levels and pulsatility index (PI) of medial cerebral arteries (MCA) either in 6 h of age or at the 4th day old independently predicted adverse outcomes. Conclusions: Blood lactate, which is a common accessible test at the hospital and MCA PI on cerebral ultrasound could predict adverse outcomes in asphyxiated infants receiving therapeutic hypothermia.