Objective: Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. Method: Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP. Results: The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway. Conclusion: ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.

Background: The direct anterior approach for total hip arthroplasty (THA) has specific advantages, but injury to the tensor fasciae lata muscle (TFLM) remains a concern. This injury in part negates some of the advantages of the intermuscular approach, because injury of the muscle fibers of the TFLM can lead to less satisfactory clinical results. Thus, in this study, we propose an intraoperative method to protect the TFLM and demonstrate its feasibility. Methods: Fifty-six patients undergoing THA by the direct anterior approach were divided randomly into two groups. In group A, the TFLM was protected by an autogenous tissue “pad” created from the anterior capsule of the joint which protect the TFLM from direct contact with the retractors. In group B, the operation was carried out with no protection of the TFLM except the attempt by the surgeons to consciously avoid injury of the TFLM. We evaluated magnitude of changes in the muscle cross-sectional area (MSCA) and fatty atrophy (FA) by magnetic resonance imaging. The differences in blood hemoglobin and serum levels of myoglobin, lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were compared at different time, postoperatively. The Harris hip score, postoperative drainage volume and visual analogue scores (VAS) were compared between the two groups. Results: LDH, CPK and myoglobin in group B were significantly higher than group A at 8, 24, and 48 h after the surgery. (p < 0.05) Compared to the group A, the decrease of hemoglobin in group B displayed significantly at 24 and 48 h after surgery. (P < 0.05) The significantly increased MSCA and FA of TFLM were demonstrated in group B. The PDV and VAS in group B were significantly higher than group A. (P < 0.05) The Harris score in group A was significantly higher than group B (P < 0.05) one month after surgery, but there was no significant difference six months later. Conclusions: Using the anterior capsule of the hip joint as an autogenous, protective capsular tissue pad to limit the trauma to the TFLM during a direct anterior approach to THA is an effective method to protect the TFLM and improve the clinical effect. Trial registration: ChiCTR: ChiCTR1900025173. Retrospectively registered August 15, 2019.

With the patient in a constant supine position, elevation of the femur in THA (DAA) provides a more intuitive and conducive location of the acetabulum for the correct placement of the acetabular prosthesis, but elevation of the femur for broaching becomes more challenging. The purpose of this study is to analyze the restriction of the ischiofemoral ligament and short external rotation muscles, and its effect on the elevation of the proximal femur in the DAA. The study subjects comprised 5 freshly frozen cadavers with 10 normal hips. All of the anatomic dissections of all of the hips were performed through the DAA. The ischiofemoral ligament, piriformis, conjoint tendon, and external obturator were successively resected. All of the proximal femurs of the specimens were levered by a point tip curved retractor that was connected with a dynamometer. Through preliminary measurements, an applied force of 80 N was adopted and maintained on the curved retractor. The experiment was repeated to measure the displacement of the proximal femur being raised after the posterior structures of the hip joint had been resected in a stepwise fashion. The displacement of the retractor was recorded, and the data were then analyzed. The distance significantly increased after the ischiofemoral ligament was severed (P < 0.001). A prominent increase was demonstrated after the conjoint tendons were severed (P < 0.001). The distance insignificantly increased after the piriformis was severed (P > 0.05). After the obturator externus was cut off, the distance increased by an insignificant amount (P > 0.05). In DAA, the ischiofemoral ligament contributed stability when the femur was being raised. The main contribution of restriction was provided by the conjoint tendon. The tendons of the obturator externus muscle and piriformis muscle did not provide any significant restriction when the femur was being raised.

Studies have demonstrated that chondrocyte senescence is involved in the pathological progression of osteoarthritis. This study aimed to investigate the effect of TF3 on chondrocyte senescence and its underlying molecular mechanism. Primary chondrocytes were isolated from mice, and senescence-related markers, mitochondrial metabolism levels, and the expression of the FGF7/Keap1-NRF2-related pathway were examined using CCK-8 assay, Western blot, β-galactosidase staining, and fluorescence staining. RNA sequencing and molecular docking were further employed to explore the mechanisms by which TF3 inhibits chondrocyte senescence. A mouse model of destabilization of the medial meniscus (DMM) was established, and the anti-senescence and cartilage protective effects of TF3 were evaluated through H&E staining, immunohistochemistry, micro-CT, and Safranin O/Fast Green staining. The results showed that TF3 suppressed the expression of senescence-associated proteins, including p16^Ink4a, p21, IL-6, and MMP13, while promoting the expression of Coll2a1 in IL-1β induced cell senescence model. Additionally, TF3 reduced β-galactosidase activity and alleviated DNA damage. RNA sequencing and experimental findings revealed that the anti-senescence effect of TF3 might be related to the regulation of oxidative stress and mitochondrial metabolism. Furthermore, the FGF7 and Keap1/NRF2 pathway were involved in TF3-mediated inhibition of chondrocyte senescence. NRF2 knockdown and exogenous rFGF7 supplementation abrogated the protective effects of TF3 against chondrocyte senescence. Animal experiments further confirmed that TF3 exerted anti-senescence effects and delayed joint degeneration. This study reveals important molecular mechanisms by which TF3 inhibits chondrocyte senescence and retards OA progression, suggesting that TF3 may serve as a potential novel therapeutic strategy for OA.