Gut-bone axis research: unveiling the impact of gut microbiota on postmenopausal osteoporosis and osteoclasts through Mendelian randomization.

Background: Postmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention. Methods: We employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287. Results: The outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis. Conclusion: This study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis.

LINC01133 regulates MARCKS expression via sponging miR-30d-5p to promote the development of lung squamous cell carcinoma.

LncRNAs are vital regulators for lung squamous cell carcinoma (LUSC). However, the detailed role that LINC01133 plays in LUSC is unclear. This work sought to explore the potential function of LINC01133.Levels of LINC01133, miR-30d-5p, and MARCKS were separately tested in both tissues and cells using qRT-PCR. Proliferation was assessed through MTT experiment and apoptosis was detected upon flow cytometry. Transwell experiments were implemented to evaluate migratory and invasive abilities. The interaction between two genes was affirmed through luciferase reporter assay and RNA pull-down experiment. Western blotting measured the protein level of MARCKS. Animal models were established and tissues were taken for IHC analysis of MARCKS and Ki67.LINC01133 was elevated in LUSC and its downregulation could suppress proliferation, migration and invasion but induced apoptosis. LINC01133 interacted with and regulated the binding of miR-30d-5p to MARCKS. LINC01133/miR-30d-5p axis mediated proliferation, apoptosis, migration and invasion in LUSC cells, as well as modulated tumor growth in animal models. LINC01133 interacted with miR-30d-5p to modulate MARCKS expression, contributes to promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. These findings could provide possible therapeutic targets in view of LUSC treatment in the future.

TRPV Channels in Osteoarthritis: A Comprehensive Review.

Osteoarthritis (OA) is a debilitating joint disorder that affects millions of people worldwide. Despite its prevalence, our understanding of the underlying mechanisms remains incomplete. In recent years, transient receptor potential vanilloid (TRPV) channels have emerged as key players in OA pathogenesis. This review provides an in-depth exploration of the role of the TRPV pathway in OA, encompassing its involvement in pain perception, inflammation, and mechanotransduction. Furthermore, we discuss the latest research findings, potential therapeutic strategies, and future directions in the field, shedding light on the multifaceted nature of TRPV channels in OA.

Efficacy and safety of odanacatib for osteoporosis treatment: a systematic review and meta-analysis.

PURPOSE: Osteoporosis is a metabolic bone disease that commonly results in middle-aged and elderly people following fractures. Odanacatib (ODN), a potential osteoporosis medication, was stopped in the Long-term Odanacatib Fracture Trial (LOFT) phase III study because it increased the risk of stroke. Herein, we conducted a systematic review and meta-analysis to further assess the efficacy and safety of ODN in osteoporosis treatment. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Web of Science, using the core search terms "osteoporosis" and "odanacatib." The primary outcomes were the percentage change in markers of bone turnover and bone formation as well as that in the bone mineral density (BMD) of the lumbar spine, hip, femoral neck, and greater trochanter. The secondary outcome was the risk of adverse events (AEs), used to explore the safety of ODN. RESULTS: Ten articles-all double-blinded, randomized, placebo-controlled trials-were included. All trials were considered to be of high quality if they met the inclusion and exclusion criteria. We found that ODN increases BMD in the lumbar spine, total hip, and femoral neck, whereas it decreases the concentration of serum C-telopeptides of type I collagen (sCTx) and urinary N-telopeptide/creatinine ratio (uNTx/Cr). We found no significant differences in total, drug-related, serious, or skin AEs between the ODN and control groups. However, significant differences in fracture and stroke AEs were found between the ODN and control groups. CONCLUSION: ODN is an appealing long-term osteoporosis treatment method; however, further research should focus on the potential increased risk of fracture and stroke.

Strategies for promoting tendon-bone healing: Current status and prospects.

Tendon-bone insertion (TBI) injuries are common, primarily involving the rotator cuff (RC) and anterior cruciate ligament (ACL). At present, repair surgery and reconstructive surgery are the main treatments, and the main factor determining the curative effect of surgery is postoperative tendon-bone healing, which requires the stable combination of the transplanted tendon and the bone tunnel to ensure the stability of the joint. Fibrocartilage and bone formation are the main physiological processes in the bone marrow tract. Therefore, therapeutic measures conducive to these processes are likely to be applied clinically to promote tendon-bone healing. In recent years, biomaterials and compounds, stem cells, cell factors, platelet-rich plasma, exosomes, physical therapy, and other technologies have been widely used in the study of promoting tendon-bone healing. This review provides a comprehensive summary of strategies used to promote tendon-bone healing and analyses relevant preclinical and clinical studies. The potential application value of these strategies in promoting tendon-bone healing was also discussed.

Effects of Platelet-Rich Plasma on Tendon-Bone Healing After Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: To investigate the effect of platelet-rich plasma on tendon-bone healing after anterior cruciate ligament reconstruction. METHODS: This retrospective study included 85 patients (range, 18-50 years; mean age, 33.95 ± 10.53 years; male/female, 49/36) who underwent anterior cruciate ligament reconstruction using autologous hamstring tendons between August 2017 and June 2019 at our institute. The participants in the study group (n = 42) were injected with platelet-rich plasma at both ends of the tendon graft, while those in the control group (n = 43) received an injection of normal saline. Magnetic resonance imaging signal/noise quotient values of the femoral and tibial ends, knee Lysholm scores, and International Knee Documentation Committee scores were compared at 3, 6, and 12 months postoperatively. RESULTS: The signal/noise quotient values of the femoral and tibial ends in both groups were higher at 6 months than at 3 and 12 months postoperatively. The signal/noise quotient values of the tibial end were significantly lower in the platelet-rich plasma group than in the normal saline group at all follow-up time points (P < 0.05). The signal/noise quotient values of the tibial and femoral ends in both groups were significantly different at 3, 6, and 12 months postoperatively (P < 0.05). Additionally, the signal/noise quotient values of the tibia were significantly lower than those of the femur in both groups (P < 0.05). The Lysholm and International Knee Documentation Committee scores were significantly better in the platelet-rich plasma group than in the normal saline group only at 3 months postoperatively. No complications, such as knee joint infection or vascular and nerve injuries, occurred in any of the 85 patients. The knee flexion of all patients were more than 90°, and the straight degree was 0°. No joint stiffness was observed in all patients. CONCLUSION: Platelet-rich plasma can promote tendon-bone healing in grafts and can improve early postoperative knee joint function.

[Effectiveness comparison of arthroscopic intertubercular groove and open subpectoral tenodesis for long head of biceps tendon tendinopathy].

OBJECTIVE: To compare the effectiveness of arthroscopic intertubercular groove and open subpectoral tenodesis in treatment of long head of biceps tendon (LHBT) tendinopathy. METHODS: A clinical data of 80 patients with LHBT tendinopathy who were admitted between June 2013 and May 2017 and met the selection criteria was retrospectively analyzed. After cutting LHBT under arthroscopy, the arthroscopic intertubercular groove tenodesis was performed in 40 cases (group A) and open subpectoral tenodesis was performed in 40 cases (group B). There was no significant difference in the gender, age, side of the affected shoulder joint, disease duration, and preoperative pain visual analogue scale (VAS) score, Constant score, American Society of Shoulder and Elbow Surgery (ASES) score, Disability of Arm, Shoulder, and Hand (DASH) score, LHBT score (LHBS) between the two groups ( P>0.05). The operation time and the scores of shoulder joint pain and function at 12 months after operation were compared between the two groups. RESULTS: The operation time was (3.6±2.5) minutes in group A and (8.5±2.3) minutes in group B, showing a significant difference ( t=18.584, P=0.000). The incisions of the two groups healed by first intention, and there was no complication such as infection or thrombosis. All patients were followed up. The follow-up time was 24-30 months (mean, 26.0 months) in group A and 24-31 months (mean, 26.0 months) in group B. Both Speed test and Yergason test were negative at 3 months after operation. MRI showed that there was no obvious effusion around the LHTB and no dislocation of LHTB. At 12 months after operation, the VAS score, Constant score, ASES score, DASH score, and LHBS score of the two groups all improved when compared with preoperative ones ( P<0.05), and there was no significant difference in the differences before and after operation between the two groups ( P>0.05). No Popeye sign appeared during the follow-up. CONCLUSION: The arthroscopic intertubercular groove and open subpectoral tenodesis can effectively relieve shoulder pain and improve function, but the former has shorter operation time and less trauma.

[Correlation between graft maturity and knee function after anterior cruciate ligament reconstruction].

OBJECTIVE: To investigate the correlation between graft maturity and knee function after anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 50 patients who underwent ACL reconstruction with autologous tendons between August 2016 and August 2018 were included in the study. There were 28 males and 22 females, with an average age of 31.0 years (range, 18-50 years). At 6 months and 2 years after operation, the signal to noise quotient (SNQ) values of tibial and femoral ends of graft were measured by MRI, and the mean value was taken as the SNQ value of graft. The function of knee joint was evaluated by Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores. The differences in SNQ values between tibial and femoral ends were analyzed at 6 months and 2 years after operation. The correlation between SNQ value at 6 months after operation and knee function score at 2 years after operation was analyzed. According to SNQ value at 6 months after operation, the patients were divided into group A (SNQ value≥12) and group B (SNQ value<12) and the correlation between SNQ value and knee function score was further analyzed. RESULTS: All incisions healed primarily without infection or injury of blood vessels and nerves. All patients were followed up 24-28 months (mean, 26.6 months). The IKDC, Lysholm, and Tegner scores at 6 months and 2 years after operation were significantly higher than those before operation ( P<0.05), and all scores at 2 years after operation were also significantly higher than those at 6 months ( P<0.05). The SNQ values at 6 months and 2 years after operation were 12.517±6.272 and 10.900±6.012, respectively, and the difference was significant ( t=1.838, P=0.007). The SNQ values of graft at 6 months after operation were significantly different from those at 2 years after operation ( P<0.05), and the SNQ values of tibial and femoral ends of graft at the same time point were significantly different ( P<0.05). The SNQ value of 50 patients at 6 months after operation was negatively correlated with Lysholm, IKDC, and Tegner scores at 2 years after operation ( r=-0.965, P=0.000; r=-0.896, P=0.000; r=-0.475, P=0.003). The patients were divided into groups A and B according to the SNQ value, each with 25 cases; the SNQ values of the two groups at 6 months after operation were negatively correlated with Lysholm, IKDC, and Tegner scores at 2 years after operation ( P<0.05). CONCLUSION: After ACL reconstruction, the knee function scores and graft maturity of patients gradually improved. The lower the SNQ value in the early stage, the higher the knee function score in the later stage. The SNQ value of MRI in the early stage after ACL reconstruction can predict the knee function in the later stage.