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.

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.

For past two decades, p53 has been claimed as the primary sensor initiating apoptosis. Under severe cellular stress, p53 transcriptional activity activates BH3-only proteins such as Bim, Puma, or Noxa to nullify the inhibitory effects of anti-apoptotic proteins on pro-apoptotic proteins for mitochondrial outer membrane permeabilization. Cellular stress determines the expression level of p53, and the amount of p53 corresponds to the magnitude of apoptosis. However, our studies indicated that Bim and Puma are not the target genes of p53 in three cancer models, prostate cancer, glioblastoma, and osteosarcoma. Bim counteracted with Bcl-xl to activate apoptosis independently of p53 in response to doxorubicin-induced severe DNA damage in prostate cancer. Moreover, the transcriptional activity of p53 was more related to cell cycle arrest other than apoptosis for responding to DNA damage stress generated by doxorubicin in prostate cancer and glioblastoma. A proteasome inhibitor that causes protein turnover dysfunction, bortezomib, produced apoptosis in a p53-independent manner in glioblastoma and osteosarcoma. p53 in terms of both protein level and nuclear localization in combining doxorubicin with bortezomib treatment was obviously lower than when using DOX alone, inversely correlated with the magnitude of apoptosis in glioblastoma. Using a BH3-mimetic, ABT-263, to treat doxorubicin-sensitive p53-wild type and doxorubicin-resistant p53-null osteosarcoma cells demonstrated only limited apoptotic response. The combination of doxorubicin or bortezomib with ABT-263 generated a synergistic outcome of apoptosis in both p53-wild type and p53-null osteosarcoma cells. Together, this suggested that p53 might have no role in doxorubicin-induced apoptosis in prostate cancer, glioblastoma and osteosarcoma. The effects of ABT-263 in single and combination treatment of osteosarcoma or prostate cancer indicated a dual control to regulate apoptosis in response to severe cellular stress. Whether our findings only apply in these three types of cancers or extend to other cancer types remains to be explored.

The perioperative care of patients undergoing total knee arthroplasty (TKA) affects functional recovery and clinical outcomes. This study aims to introduce a patient-specific integrated education program (IEP) into the TKA clinical pathway and to evaluate patient outcomes between the intervention and control groups. We performed a two-site, two-arm, parallel-prospective controlled trial. The experiment group received an IEP incorporating verbal preoperative education, prehabilitation, multidisciplinary personalized rehabilitation during hospitalization, and supervised self-executed home-based exercise after discharge. The control group received regular TKA clinical care. We monitored the pain intensity, anxiety scores, and functional scores at six time points from the pre-operation interview to 3 months post-operation. The pain score was significantly decreased in the IEP group during hospitalization (p < 0.01) and before discharge (p < 0.05). The anxiety status was also improved after intervention in terms of state and trait anxiety inventory scores (p < 0.001) during hospitalization. The patient-reported (WOMAC) or physician-reported (American Knee Society Score) functional scores (p < 0.01 at most of the time points) all improved significantly under hospitalization. We found that the patient-specific IEP combining preoperative education, prehabilitation, the in-hospital group education class, and postoperative care navigation is effective in reducing postoperative pain, decreasing perioperative anxiety, and facilitating functional recovery following TKA.

Graft cell repopulation and tendon-bone tunnel healing are important after allograft anterior cruciate ligament reconstruction (ACLR). Freshly isolated bone marrow mononuclear cells (BMMNCs) have the advantage of short isolation time during surgery and may enhance tissue regeneration. Thus, we hypothesized that the effect of intra-articular BMMNCs in post-allograft ACLR treatment is comparable to that of cultured bone marrow stromal cells (BMSCs). A rabbit model of hamstring allograft ACLR was used in this study. Animals were randomly assigned to the BMMNC, BMSC, and control groups. Fresh BMMNCs isolated from the iliac crest during surgery and cultured BMSCs at passage four were used in this study. A total of 1 × 10⁷ BMMNCs or BMSCs in 100 µL phosphate-buffered saline were injected into the knee joint immediately after ACLR. The control group was not injected with cells. At two and six weeks post operation, we assessed graft cell repopulation with histological and cell tracking staining (PKH26), and tendon-bone healing with histological micro-computed tomography and immunohistochemical analyses for collagen I and monocyte chemoattractant protein-1 (MCP1). At two weeks post operation, there was no significant difference in the total cell population within the allograft among the three groups. However, the control group showed significantly higher cell population within the allograft than that of BM cell groups at six weeks. Histological examination of proximal tibia revealed that the intra-articular delivered cells infiltrated into the tendon-bone interface. Compared to the control group, the BM cell groups showed broader gaps with interfacial fibrocartilage healing, similar collagen I level, and higher MCP1 expression in the early stage. Micro-CT did not reveal any significant difference among the three groups. BMMNCs and BMSCs had comparable effects on cell repopulation and interfacial allograft-bone healing. Intra-articular BM cells delivery had limited benefits on graft cell repopulation and caused higher inflammation than that in the control group in the early stage, with fibrocartilage formation in the tendon-bone interface after allograft ACLR.

Micro arc oxidation (MAO) is a prominent surface treatment to form bioceramic coating layers with beneficial physical, chemical, and biological properties on the metal substrates for biomaterial applications. In this study, MAO treatment has been performed to modify the surface characteristics of AZ31 Mg alloy to enhance the biocompatibility and corrosion resistance for implant applications by using an electrolytic mixture of Ca₃(PO₄)₂ and C₁₀H₁₆N₂O₈ (EDTA) in the solutions. For this purpose, the calcium phosphate (Ca-P) containing thin film was successfully fabricated on the surface of the implant material. After in-vivo implantation into the rabbit bone for four weeks, the apparent growth of soft tissues and bone healing effects have been documented. The morphology, microstructure, chemical composition, and phase structures of the coating were identified by SEM, XPS, and XRD. The corrosion resistance of the coating was analyzed by polarization and salt spray test. The coatings consist of Ca-P compounds continuously have proliferation activity and show better corrosion resistance and lower roughness in comparison to mere MAO coated AZ31. The corrosion current density decreased to approximately 2.81 × 10⁻⁷ A/cm² and roughness was reduced to 0.622 μm. Thus, based on the results, it was anticipated that the development of degradable materials and implants would be feasible using this method. This study aims to fabricate MAO coatings for orthopedic magnesium implants that can enhance bioactivity, biocompatibility, and prevent additional surgery and implant-related infections to be used in clinical applications.