Baohuoside I Inhibits Osteoclastogenesis and Protects Against Ovariectomy-Induced Bone Loss.

Bone-resorbing osteoclasts are essential for skeletal remodelling, and the hyperactive formation and function of osteoclasts are common in bone metabolic diseases, especially postmenopausal osteoporosis. Therefore, regulating the osteoclast differentiation is a major therapeutic target in osteoporosis treatment. Icariin has shown potential osteoprotective effects. However, existing studies have reported limited bioavailability of icariin, and the material basis of icariin for anti-osteoporosis is attributed to its metabolites in the body. Here, we compared the effects of icariin and its metabolites (icariside I, baohuoside I, and icaritin) on osteoclastogenesis by high-content screening followed by TRAP staining and identified baohuoside I (BS) with an optimal effect. Then, we evaluated the effects of BS on osteoclast differentiation and bone resorptive activity in both in vivo and in vitro experiments. In an in vitro study, BS inhibited osteoclast formation and bone resorption function in a dose-dependent manner, and the elevated osteoclastic-related genes induced by RANKL, such as NFATc1, cathepsin K, RANK, and TRAP, were also attenuated following BS treatment. In an in vivo study, OVX-induced bone loss could be prevented by BS through interrupting the osteoclast formation and activity in mice. Furthermore, mechanistic investigation demonstrated that BS inhibited osteoclast differentiation by ameliorating the activation of the MAPK and NF-kB pathways and reducing the expression of uPAR. Our study demonstrated that baohuoside I could inhibit osteoclast differentiation and protect bone loss following ovariectomy.

Synergistic prognostic value of coronary distensibility index and fractional flow reserve based cCTA for major adverse cardiac events in patients with Coronary artery disease.

BACKGROUND: Coronary distensibility index (CDI), as an early predictor of cardiovascular diseases, has the potential to complement coronary computed tomography angiography (cCTA)-derived fractional flow reserve (CT-FFR) for predicting major adverse cardiac events (MACEs). Thus, the prognostic value of CT-FFR combined with CDI for MACEs is worth exploring. METHODS: Patients with a moderate or severe single left anterior descending coronary artery stenosis were included and underwent FFR and CDI analysis based on cCTA, followed up at least 1 year, and recorded MACEs. Multivariate logistic regression analysis was performed to determine independent predictors of MACEs. The area under of receiver operating characteristic (ROC) curve was used to evaluated evaluate the diagnostic performance of CT-FFR, CDI, and a combination of the two. RESULTS: All the vessel-specific data were from LAD. 150 patients were analysed. 55 (37%) patients experienced MACEs during follow-up. Patients with CT-FFR ≤ 0.8 had higher percentage of MACEs compared with CT-FFR > 0.8 (56.3% vs.7.3%, p < 0.05). Patients' CDI was significantly decreased in MACEs group compared with non-MACEs group (p < 0.05). Multivariate analysis revealed that diabetes (p = 0.025), triglyceride (p = 0.015), CT-FFR ≤ 0.80 (p = 0.038), and CDI (p < 0.001) are independent predictors of MACEs. According to ROC curve analysis, CT-FFR combined CDI showed incremental diagnostic performance over CT-FFR alone for prediction of MACEs (AUC = 0.831 vs. 0.656, p = 0.0002). CONCLUSION: Our study provides initial evidence that combining CDI with CT-FFR shows incremental discriminatory power for MACEs over CT-FFR alone, independent of clinical risk factors. Diabetes and triglyceride are also associated with MACEs.

The efficacy of platelet rich plasma on anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

Anterior cruciate ligament (ACL) rupture is a common musculoskeletal injury, most frequently affecting young and physically active patients. Platelet-rich plasma (PRP) has been widely used in ACL reconstruction to augment the graft healing. However, high-level studies addressing its clinical efficacy could not reach a consensus. In this study, we assess the efficacy of PRP on pain relief, functional improvement along with radiological changes in patients who underwent ACL reconstruction. We performed comprehensive literature search and included 17 RCTs containing 970 participants who underwent ACL reconstruction. The combined data showed significant difference between PRP and control with regard to VAS score (MD: -1.12, 95% CI -1.92, -0.31; P = .007), subjective IKDC score (MD: 6.08, 95% CI 4.39, 7.77; P < .00001) and Lysholm score (MD: 8.49, 95% CI 1.63, 15.36; P = .02) by postoperative 6 months, but only pain reduction was deemed clinically important. At the end of one year's follow-up, no clinically meaningful improvement in VAS (MD: -0.47, P = .04), subjective IKDC score (MD: 3.99, P = .03), Lysholm score (MD: 2.30, P = .32), objective IKDC score (RR: 1.03, P = .09) and knee joint laxity (MD: 0.17, P = .28) was seen. In terms of radiological findings, about one-third of the studies favored PRP to facilitate the graft healing, improve the harvest site morbidity and prevent tunnel widening. In summary, moderate quality of evidence suggested that PRP could provide short-term but not long-term clinically important pain reduction.

Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. METHODS: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. RESULTS: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. CONCLUSIONS: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

Association of ITGAV polymorphisms and risk of rheumatoid arthritis: evidence from a meta-analysis.

OBJECTIVE: Currently published papers regarding the relationship between integrin alpha V (ITGAV) gene polymorphisms and rheumatoid arthritis (RA) are contradictory. The aim of this meta-analysis was to evaluate the associations between the ITGAV gene polymorphisms and RA risk. METHODS: Comprehensive literature search based on four electronic databases was applied to retrieve all related data. Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess associations between ITGAV gene polymorphisms and RA. RESULTS: Six articles involving 5794 RA patients and 5297 healthy controls were included in this meta-analysis. The combined data indicated that rs3911238, rs3738919, rs3768777, and rs10174098 in ITGAV gene were not associated with RA risk in the overall population. However, stratification analysis by ethnicity suggested that rs3768777 was related with risk of RA among Caucasian population (OR 3.51, 95%CI 2.06, 5.97; P < 0.0001), but not among Asian population (OR 1.06, 95%CI 0.67, 1.69; P = 0.81). CONCLUSIONS: Our meta-analysis confirmed that the ITGAV gene rs3768777 polymorphisms might be a risk factor among Caucasians. However, larger-scale studies in Caucasian population are still warranted to confirm the findings of our study.

Urolithin a attenuates IL-1ß-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes.

BACKGROUND: Osteoarthritis (OA) is characterized by inflammation and extracellular matrix (ECM) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults. Urolithin A (UA) has been widely reported for its anti-inflammatory properties in several chronic diseases. However, the effects of UA on OA remain unclear. The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1ß (IL-1ß)-induced chondrocytes. RESULTS: No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1ß stimulation in micromasses. Moreover, UA promoted the expression of anabolic factors including Sox-9, Collagen II, and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) in rat chondrocytes. Protective effects of UA were also observed in ex vivo organ culture of articular cartilage. Mechanistically, IL-1ß significantly activated and upregulated the expression of p-ERK 1/2, p-JNK, p-P38, and p-P65, while UA protected chondrocytes against IL-1ß-induced injury by activating the mitogen-activated kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways. CONCLUSION: Our results provide the evidence that UA could attenuate IL-1ß-induced cell injury in chondrocytes via its anti-inflammatory action. UA may be a promising therapeutic agent in the treatment of OA.