Huichao Wang

Baicalein ameliorates inflammatory-related apoptotic and catabolic phenotypes in human chondrocytes.

Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. In OA, pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α can trigger the caspase cascade to promote apoptosis and activate NF-κB to induce catabolic factors in chondrocytes. Here, the anti-apoptotic and anti-catabolic effects of baicalein on human OA chondrocytes treated by a mixture of IL-1β and TNF-α (IT) were investigated in vitro. In cultured chondrocytes, baicalein pretreatment attenuated apoptosis in a concentration-dependent manner in response to IT stimulation. Mechanistically, the anti-apoptotic effects of baicalein result from inhibition of nitric oxide production and downstream caspase signaling pathway. Moreover, administration of baicalein significantly reduced matrix metalloproteinase (MMP) 3 and MMP13 secretion in chondrocytes stimulated with IT. The anti-catabolic effects of baicalein were further demonstrated by the recovery of the glycosaminoglycan and type II collagen (COLII) deposition by histological analysis in IT-treated mouse articular cartilage explants. These findings suggest that baicalein might be a promising novel therapeutic agent for OA by virtue of its suppression of apoptosis and MMP secretion in OA chondrocytes.

Increased microRNA-93-5p inhibits osteogenic differentiation by targeting bone morphogenetic protein-2.

Background and purpose Trauma-induced osteonecrosis of the femoral head (TIONFH) is a major complication of femoral neck fractures. Degeneration and necrosis of subchondral bone can cause collapse, which results in hip joint dysfunction in patients. The destruction of bone metabolism homeostasis is an important factor for osteonecrosis. MicroRNAs (miRNAs) have an important role in regulating osteogenic differentiation, but the mechanisms underlying abnormal bone metabolism of TIONFH are poorly understood. In this study, we screened specific miRNAs in TIONFH by microarray and further explored the mechanism of osteogenic differentiation. Design Blood samples from patients with TIONFH and patients without necrosis after trauma were compared by microarray, and bone collapse of necrotic bone tissue was evaluated by micro-CT and immunohistochemistry. To confirm the relationship between miRNA and osteogenic differentiation, we conducted cell culture experiments. We found that many miRNAs were significantly different, including miR-93-5p; the increase in this miRNA was verified by Q-PCR. Comparison of the tissue samples showed that miR-93-5p expression increased, and alkaline phosphatase (ALP) and osteopontin (OPN) levels decreased, suggesting miR-93-5p may be involved in osteogenic differentiation. Further bioinformatics analysis indicated that miR-93-5p can target bone morphogenetic protein 2 (BMP-2). A luciferase gene reporter assay was performed to confirm these findings. By simulating and/or inhibiting miR-93-5p expression in human bone marrow mesenchymal stem cells, we confirmed that osteogenic differentiation-related indictors, including BMP-2, Osterix, Runt-related transcription factor, ALP and OPN, were decreased by miR-93-5p. Conclusion Our study showed that increased miR-93-5p in TIONFH patients inhibited osteogenic differentiation, which may be associated with BMP-2 reduction. Therefore, miR-93-5p may be a potential target for prevention of TIONFH.

Analysis of damage in relation to different classifications of pre-collapse osteonecrosis of the femoral head

Objective This study aimed to investigate the damage pattern of the stress transfer path (STP) for the Japanese Investigation Committee (JIC) classification of pre-collapse osteonecrosis of the femoral head. We aimed to provide a specific biomechanical basis for treatment decisions of each subtype. Methods Five computational models were used in the experiment. Different necrotic classifications were simulated based on the JIC classification system. Damage patterns of the STP were used for qualitative assessment and average stresses were used for quantitative analysis. Results The STP of type A showed a strong similarity to the healthy level, which was consistent with the bone density distribution in X-rays and previous simulations results. The damaged area of principal stress of type B was approximately 25% of the healthy level. The STPs of types C1 and C2 were broken and the damaged areas of principal stress were more than 50% of the healthy level. The efficiency of stress transfer was reduced. Conclusions These results indicate that the damage patterns and stress transfer efficiency of the femoral head are associated with necrotic classifications.

Downregulated miR-29a/b/c during Contact Inhibition Stage Promote 3T3-L1 Adipogenesis by Targeting DNMT3A.

Differentiation of 3T3-L1 cells into adipocytes involves a highly-orchestrated series of events including contact inhibition (CI), clonal expansion, growth arrest, and terminal differentiation. Recent study demonstrated that 3T3-L1 preadipocytes will not be differentiated into mature adipocytes without CI stage, which indicated that CI stage plays an important role during 3T3-L1 adipogenesis. However, the molecular mechanism is not yet fully understood. In the present study, we found that the expression level of miR-29a/b/c was decreased and the expression of DNMT3A was up-regulated during CI stage, respectively. Furthermore, overexpression of miR-29a/b/c during CI stage inhibits adipogenesis significantly but not at other stages. In addition, miR-29a/b/c repressed DNMT3A expression by directly targeting its 3’ untranslated region (3’ UTR). Our data reveal a novel mechanism of miR-29a/b/c in the regulation of adipogenesis.

Systematic Review of Three Electrical Stimulation Techniques for Rehabilitation After Total Knee Arthroplasty

BACKGROUND The comparative effectiveness of neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and electroacupuncture (EA) for improving patient rehabilitation following total knee arthroplasty (TKA) is controversial. Therefore we conducted this systematic review to assess the available evidence. METHODS The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Data were extracted and qualitatively synthesized for several outcomes. RESULTS Data were analyzed from 17 randomized controlled trials involving 1285 procedures: 8 NMES studies (608 procedures), 7 TENS studies (560 procedures), and 2 EA studies (117 procedures). Qualitative analysis suggested that NMES was associated with higher quadriceps strength and functional recovery after TKA. Recovery benefits were maximal when the stimulation was performed once or twice a day for 4-6 weeks at an intensity of 100-120 mA and frequency of 30-100 Hz. The electrode should be sufficiently large (100-200 cm2) to reduce discomfort. TENS at an intensity of 15-40 mA and frequency of 70-150 Hz provided effective analgesia after TKA. EA at an intensity of 2 mA and frequency of 2 Hz may also provide postoperative analgesia of TKA. CONCLUSION As adjunct modalities, NMES and TENS can effectively improve rehabilitation after TKA without triggering significant intolerance, and maximal benefits depend on optimized parameters and intervention protocols. EA may be an effective adjunct modality for analgesia after TKA.