Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells.

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

Epimedium-Curculigo herb pair enhances bone repair with infected bone defects and regulates osteoblasts through LncRNA MALAT1/miR-34a-5p/SMAD2 axis.

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-ß signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-ß/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.

α-Solanine attenuates chondrocyte pyroptosis to improve osteoarthritis via suppressing NF-κB pathway.

α-Solanine has been shown to exhibit anti-inflammatory and anti-tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study aimed to evaluate the therapeutic effects of α-solanine on OA development in a mouse OA model. The OA mice were subjected to varying concentrations of α-solanine, and various assessments were implemented to assess OA progression. We found that α-solanine significantly reduced osteophyte formation, subchondral sclerosis and OARSI score. And it decreased proteoglycan loss and calcification in articular cartilage. Specifically, α-solanine inhibited extracellular matrix degradation by downregulating collagen 10, matrix metalloproteinase 3 and 13, and upregulating collagen 2. Importantly, α-solanine reversed chondrocyte pyroptosis phenotype in articular cartilage of OA mice by inhibiting the elevated expressions of Caspase-1, Gsdmd and IL-1ß, while also mitigating aberrant angiogenesis and sensory innervation in subchondral bone. Mechanistically, α-solanine notably hindered the early stages of OA progression by reducing I-κB phosphorylation and nuclear translocation of p65, thereby inactivating NF-κB signalling. Our findings demonstrate the capability of α-solanine to disrupt chondrocyte pyroptosis and sensory innervation, thereby improving osteoarthritic pathological progress by inhibiting NF-κB signalling. These results suggest that α-solanine could serve as a promising therapeutic agent for OA treatment.

Multiple intra-articular injections of autologous stromal vascular fractions for the treatment of multicompartmental osteoarthritis in both the tibiofemoral and patellofemoral joint: a single-blind randomized controlled study.

BACKGROUND: Multicompartmental osteoarthritis (MOA) in both tibiofemoral and patellofemoral joints is a more commonly occurring, but neglected, clinical condition, and we examined the short-term safety and efficacy of autologous stromal vascular fractions (SVFs) for MOA using a single-blind, prospective, randomized, placebo-controlled trial. METHODS: Seventy MOA patients were recruited and randomly assigned to the SVF group and hyaluronic acid (HA) group (control group). The scores of visual analog scale, the Western Ontario and McMaster University Osteoarthritis Index, and the Samsung Medical Center patellofemoral scoring system were assessed and compared between the two groups 3, 6 and 12 months after treatment. RESULTS: The SVF group had significantly better visual analog scale scores than the HA group at 6 and 12 months after treatment and had better Western Ontario and McMaster University Osteoarthritis Index scores than the HA group only at 6 months after treatment. For Samsung Medical Center patellofemoral scoring system of the patellofemoral joint, the SVF group had significantly better scores than the control group at all postoperative time points. The proportion of patients whose visual analog scale and Western Ontario and McMaster University Osteoarthritis Index scores were above the minimal clinically important improvement was higher in the SVF group than in the HA group in the majority of assessments. The improvement of bone marrow by SVF treatment was significantly better than that of the HA group as observed by pre- and postoperative Magnetic resonance imaging (MRI). CONCLUSIONS: Multiple intra-articular injection of autologous SVF reduces pain and improves function in the short term in patients with early or midstage MOA. However, there was heterogeneity in the improvement of overall knee and isolated patellofemoral joint after treatment.

Crohn's disease in hemophilic arthropathy patient: a case report.

Crohn's disease (CD) is an inflammatory bowel disease affecting the digestive tract, the incidence of which is on the rise worldwide. The most common clinical manifestation of hemophilia is arthropathy secondary to recurrent joint effusions and chronic synovitis. This article reports on a rare 25-year-old male patient with both hemophilic arthropathy and Crohn's disease who was at risk for pathogenic gastrointestinal bleeding. After undergoing endoscopic pathologic testing and genetic testing, a multidisciplinary expert work-up of a treatment and nutritional plan was performed. The patient improved clinically and adhered to conservative treatment. This case report is the first report of this rare co-morbidity, demonstrating the highly pathogenic mutation locus and summarizing the clinical experience of early diagnosis and treatment.

Modified osteochondral autograft transplantation for steroid-induced osteonecrosis of femoral head in idiopathic thrombocytopenic purpura: a case report and literature.

Osteochondral autograft transplantation (OAT) has been commonly applied in the knee and ankle while the technique has not yet been a popularity in the femoral head. In this article, we present a 28-year-old female patient, who has a history of 1-year-use of glucocorticoid in the treatment of idiopathic thrombocytopenic purpura, with steroid-induced osteonecrosis of the femoral head (SONFH). She underwent surgical hip dislocation, osteochondroplasty, OAT, and internal fixation. Her Harris Hip Score improved from 64 to 82 in 36 months to follow-up. The case is valuable considering that a single, instead of several, 1.5 cm autograft was harvested from the non-bearing part of the same femoral head. This modification dispensed with the need of surgery for harvesting autograft from knee or ankle and reduced the structural vulnerability brought by the multihole donor part of the femoral head.

Factors influencing periprosthetic bone mineral density in total knee arthroplasty: a systematic review.

INTRODUCTION: Following total knee arthroplasty (TKA), there is a significant decline in periprosthetic bone mineral density (BMD), potentially resulting in complications such as prosthetic loosening, periprosthetic fracture, and influencing the postoperative recovery. The objective of this study was to summarize the factors influencing periprosthetic BMD in TKA from existing studies. METHODS: A comprehensive systematic search was performed in 4 databases: Pubmed, Embase, Web of Science, and Cochrane Library. The last search was carried out on October 12, 2023. We used the keywords ''total knee arthroplasty'', ''bone mineral density'' and each of them combined with ''tibia'' and ''femur'' to identify all relevant articles reporting about potential impact factors influencing the periprosthetic BMD in patients after TKA. RESULTS: Out of 1391 articles, 22 published from 2001 to 2023 were included in this systematic review. Following eligibility screening, six significant categories affecting periprosthetic BMD were recognized: prosthesis type, design of stem, coating, body weight, cement, and peg distance. CONCLUSION: Mobile-bearing prostheses, modular polyethylene design, short stems, cruciform stems, avoidance of bone cement, higher body mass index, titanium nitride coating, and a smaller medial peg distance could potentially benefit periprosthetic BMD. Comprehensive consideration of diverse factors influencing periprosthetic BMD before surgery and collaboration with post-operative drug therapy are essential. TRIAL REGISTRY: The PROSPERO registration number is CRD42023472030.

Etiology, pathology, and treatment of osteonecrosis of the femoral head in adolescents: A comprehensive review.

Femoral head necrosis is a common refractory disease in orthopedics, and shows a trend of getting younger. The occurrence of femoral head necrosis in adolescents is related to the use of glucocorticoids, autoimmune diseases, trauma, and other factors. Because adolescent patients are in the period of physical development, high activity requirements, and have fertility needs in the future, treatment is relatively difficult. Early artificial joint replacement may have problems such as wear and loosening, so total hip replacement is not the preferred treatment for adolescent patients with femoral head necrosis. This article will elaborate the research progress of femoral head necrosis in adolescents from 3 aspects, and summarize the benefits and side effects of core decompression combined with autologous stem cell transplantation in the treatment of early femoral head necrosis, so as to provide clinical ideas for the treatment of femoral head necrosis in adolescents.

Risk of low bone mineral density in patients with haemophilia: a systematic review and meta-analysis.

INTRODUCTION: Patients with haemophilia (PWH) may have lower bone mineral density (BMD). The risk of low BMD in PWH has not been comprehensively analysed. This study aimed to examine the risk of low BMD and changes in BMD in PWH. METHODS: A comprehensive systematic search was performed in 4 databases: PubMed, Embase, Web of Science, and Cochrane Library. The last search was carried out on 11 December 2022. Review Manager 5.4 and Stata 16 were used for meta-analysis. Odds ratios were calculated by the incidence of low BMD between the haemophilia and control groups in each study. A meta-analysis of the odds ratios for each study was performed to estimate pooled odds ratios. Fixed effects models or random effects models were used to assess outcomes. Heterogeneity was evaluated using Higgins' I2. Subgroup analysis and sensitivity analysis were performed to interpret the potential source of heterogeneity. A funnel plot, Egger's regression test, and the trim-and-fill method were used to assess publication bias. RESULTS: 19 of 793 studies, published between 2004 and 2022, that were identified by search strategy were included in this meta-analysis. The risk for low BMD was approximately four times higher compared to controls. PWH have significantly lower lumbar spine, femoral neck, and total hip BMD. Subgroup analysis showed that the risk of low BMD did not increase significantly in developed countries. Very low heterogeneity was observed in the meta-analysis of the risk of low BMD. The result from Egger's regression test suggested that there may be publication bias. However, the meta-analysis results did not alter after the trim-and-fill correction and the findings were robust. CONCLUSION: Haemophilia was associated with an increased risk of low BMD. However, the risk of low BMD did not increase significantly in developed countries. And BMD was reduced in PWH, regardless of age, region, or economic ability. For PWH, our concerns should extend beyond bleeding and osteoarthritis to encompass BMD starting at a young age.

miRNA-seq analysis of high glucose induced osteoblasts provides insight into the mechanism underlying diabetic osteoporosis.

The present study aims to explore the etiology of Diabetic osteoporosis (DOP), a chronic complication associated with diabetes mellitus. Specifically, the research seeks to identify potential miRNA biomarkers of DOP and investigated role in regulating osteoblasts. To achieve this, an animal model of DOP was established through the administration of a high-sugar and high-fat diet, and then injection of streptozotocin. Bone microarchitecture and histopathology analysis were analyzed. Rat calvarial osteoblasts (ROBs) were stimulated with high glucose (HG). MiRNA profiles of the stimulated osteoblasts were compared to control osteoblasts using sequencing. Proliferation and mineralization abilities were assessed using MTT assay, alkaline phosphatase, and alizarin red staining. Expression levels of OGN, Runx2, and ALP were determined through qRT-PCR and Western blot. MiRNA-sequencing results revealed increased miRNA-702-5p levels. Luciferase reporter gene was utilized to study the correlation between miR-702-5p and OGN. High glucose impaired cell proliferation and mineralization in vitro by inhibiting OGN, Runx2, and ALP expressions. Interference with miR-702-5p decreased OGN, Runx2, and ALP levels, which were restored by OGN overexpression. Additionally, downregulation of OGN and Runx2 in DOP rat femurs was confirmed. Therefore, the miRNA-702-5p/OGN/Runx2 signaling axis may play a role in DOP, and could be diagnostic biomarker and therapeutic target for not only DOP but also other forms of osteoporosis.

How Do Muscle Function and Quality Affect the Progression of KOA? A Narrative Review.

Knee osteoarthritis (KOA) is widely recognized as a chronic joint disease characterized by degeneration of knee cartilage and subsequent bone hyperplasia. However, it is important to acknowledge the significant role of muscles in the development and progression of KOA. Muscle function (MF) and muscle quality (MQ) are key factors in understanding the involvement of muscles in KOA. Quantitative indices such as muscle mass, muscle strength, muscle cross-sectional area, muscle thickness, and muscle fatigue are crucial in assessing MF and MQ. Despite the growing interest in KOA, there is a scarcity of studies investigating the relationship between muscles and this condition. This review aims to examine the commonly used indices and measurement methods for assessing MF and MQ in clinical settings, while also exploring the association between muscles and KOA. Furthermore, this article highlights the importance of restoring MF and MQ to enhance symptom management and improve the quality of life for patients with KOA.

The association between weight-adjusted-waist index and sarcopenia in adults: a population-based study.

This study aims to investigate the relationship between weight-adjusted-waist index (WWI), a new body index, and sarcopenia, while also assessing the potential of WWI as a tool for screening sarcopenic patients. The cross-sectional study involved adults who possessed complete data on WWI and appendicular skeletal muscle mass from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Surveys. Weighted multivariate regression and logistic regression analyses were employed to explore the independent relationship between WWI and sarcopenia. The study included 26,782 participants. The results showed that WWI demonstrated a positive correlation with sarcopenia risk. In the fully adjusted model, with each 1 unit increase in WWI, the risk of developing sarcopenia rose 14.55 times higher among males (OR: 14.55, 95% CI 12.33, 17.15) and 2.86 times higher among females (OR: 2.86, 95% CI 2.59, 3.15). The optimal cutoff values of WWI for sarcopenia were 11.26 cm/√kg for males and 11.39 cm/√kg for females. Individuals with a higher WWI have an increased risk of developing sarcopenia, and a high WWI functions as a risk factor for sarcopenia. Assessing WWI could assist in identifying individuals at risk of sarcopenia.

Comparing the Efficacy of Antiosteoporotic Drugs in Preventing Periprosthetic Bone Loss Following Total Hip Arthroplasty: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Periprosthetic bone loss is a well-known phenomenon following total hip arthroplasty (THA). However, the choice of drugs for prevention remains controversial. Therefore, the aim of this study was to determine the best drug to treat periprosthetic bone loss by comparing changes in bone mineral density (BMD) at different times after THA. METHODS: A comprehensive search of five databases and two clinical trial registration platforms was undertaken from their inception through to August 31, 2023 to identify eligible randomized controlled trials. A Bayesian network meta-analysis (NMA) was carried out for calculating the standardized mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the BMD in calcar (Gruen zone 7) at 6 months, 12 months, and 24 months and over. RESULTS: Twenty-nine trials involving 1427 patients and 10 different interventions were included. The results demonstrated that at 6 months, denosumab had the highest ranking (SUCRA = 0.90), followed by alendronate (SUCRA = 0.76), and zoledronate (SUCRA = 0.73). At 12 months, clodronate ranked highest (SUCRA = 0.96), followed by denosumab (SUCRA = 0.84) and teriparatide (SUCRA = 0.82). For interventions with a duration of 24 months and over, denosumab had the highest SUCRA value (SUCRA = 0.96), followed by raloxifene (SUCRA = 0.90) and zoledronate (SUCRA = 0.75). CONCLUSION: Investigating the existing body of evidence revealed that denosumab demonstrates potential as an intervention of superior efficacy at the three specifically examined time points. However, it remains crucial to conduct further research to confirm these findings and determine the most effective treatment strategy.

Bleeder's Femur: The Proximal Femoral Morphology in Hemophilic Patients Who Underwent Total Hip Arthroplasty.

INTRODUCTION: Patients with hemophilia (PWH) constantly suffer hemarthrosis, which leads to deformity of the hip joint. Therefore, PWH who are going to receive total hip arthroplasty (THA) should be exclusively treated before the surgery with careful measurement of their proximal femur. Hence, we conducted a retrospective study to explore the anatomical parameters of and differences in the proximal femur in hemophilic patients who underwent THA. METHODS: The retrospective study comprised data of adult patients who received total hip arthroplasty from 2020 to 2022 in the research center. Patients having a diagnosis of hemophilic arthritis and received THA were included in experimental group, and patients with hip arthritis or femoral head necrosis were taken as control group. Parameters including femoral offset, neck-shaft angle (NSA), medullary cavity of 20 mm above mid-lesser trochanter level (T+20), mid-lesser trochanter level (T), and 20 mm blow it (T-20), and canal flare index (CFI), femoral cortical index (FCI) were measured on X-ray and CT images with PACS by two independent doctors. Data was analyzed by SPSS 20. Kolmogorov-Smirnov test was used to test data normality. Student's t-test was performed between PWH and control group. p < 0.05 was considered statistically significant. RESULTS: Among the 94 hips, 39 (41.5%) were included in group hemophilia and 55(58.5%) in control group. The mean age of the patients was 49.36 ± 12.92 years. All cases were male patients. Data demonstrated significantly smaller femoral cortical index (FCI), femoral offset, medullary cavity of 20 mm above mid-lesser trochanter level, mid-lesser trochanter level, and 20 mm below it, and neck-shaft angle (NSA) was obviously larger in PWH than control group (p < 0.05). No significant difference was found in canal flare index (CFI). CONCLUSION: Hemophilic patients undergoing THA were prone to longer and thinner proximal femur. Preoperative morphological analysis of femur is recommended.

Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study.

Purpose: To explore the effect of AFN on knee function and complications in patients after TKA. Methods: We evaluated 150 patients undergoing unilateral TKA, specifically including 102 patients with varying degrees of AFN after selection. They were divided into four groups based on AFN grade. About 48 patients did not produce AFN, 63 patients were grade I, 29 patients were grade II, and 10 patients were grade III. All patients were followed up for 24 months, and knee function, pain, complications, and other indicators were compared between the four groups. Correlation analysis and regression analysis were used to study the relationship between AFN and other indicators. Results: Two cases of periprosthetic fractures (PPF) occurred in our study, with an incidence of 1.35%, which did not show a significant association with AFN. The changes in knee social score (ΔKSS), Western Ontario and McMaster Universities Osteoarthritis Index (ΔWOMAC), and postoperative anterior knee pain visual analog scale (VAS) score were higher in patients with AFN than in those without. Particularly, grades II and III AFN demonstrated superior efficacy. Pearson's correlation analysis showed that AFN grade is positively correlated with both ΔKSS and ΔWOMAC (r = 0.44, P < 0.001), and AFN grade had a negative correlation with the anterior knee pain VAS (r = -0.250, P < 0.05). In linear regression analysis, AFN grade was positively correlated with both ΔKSS (ß = 5.974, 95% CI: 3.968-7.981, P < 0.001) and ΔWOMAC (ß = 6.356, 95% CI: 4.223-8.490, P < 0.001). Besides that, there was a negative correlation between AFN grade and anterior knee pain (ß = 5.974, 95% CI: 3.968-7.981, P < 0.05). Conclusion: Patients with grade II and III AFN who underwent TKA exhibited better knee function and lower levels of anterior knee pain post-surgery.

Global burden and epidemic trends of gout attributable to high body mass index from 1990 to 2019.

Introduction: Gout is an inflammatory and metabolic disease characterized by arthritis and elevation of the serum uric acid (SUA) level. More and more studies have shown that high body mass index (BMI) has become one of the most important risk factors for gout. Material and methods: We used the data of gout burden attributed to high body mass index (BMI) from global burden of disease (GBD) study 2019 to provide insights for reducing the global burden of gout. Results: From 1990 to 2019, the prevalence and DALYs of gout caused by high BMI worldwide has been increasing. The burden of gout caused by high BMI is heavier in the elderly male group and regions with high SDI worldwide. Conclusions: Our findings provide evidence for the burden of gout caused by high BMI. Developing a weight management plan and lifestyle habits for groups severely affected by gout will effectively reduce the global disease and economic burden.

Corrigendum: Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-ß-Smad2/3 signaling of chondrocytes.

[This corrects the article DOI: 10.3389/fphar.2023.900205.].

Clinical Efficacy of Intra-articular Tranexamic Acid Injection in the Management of Hemophilia with Total Hip Arthroplasty: A 24-month Retrospective Cohort Study.

OBJECTIVE: Total hip arthroplasty (THA) effectively treats end-stage hemophilic hip arthropathy. Given hemophilia's unique characteristics, perioperative bleeding remains a significant risk for patients undergoing THA. Tranexamic acid (TXA), an efficient antifibrinolytic agent, may benefit the outcomes of THA for patients with hemophilia (PWH). This study aims to explore the clinical efficacy of intra-articular injection of TXA in treating perioperative bleeding in PWH and assess its additional clinical benefits. METHODS: The retrospective study comprised data of PWH who received THA from January 2015 to December 2021 in the research center. A total of 59 individuals were included in the study, divided into a TXA group (n = 31) and a non-TXA group (n = 28). We compared various parameters, including total blood loss (TBL), visible blood loss (VBL), occult blood loss (OBL), intraoperative coagulation factor VIII (FVIII) consumption, perioperative total FVIII consumption, hemoglobin (HB), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), length of hospital stay, hospitalization costs, length of surgery, total protein, activated partial thromboplastin time (APTT), D-dimer, rate of joint swelling, hip joint range of motion (ROM), visual analogue scale (VAS), and Harris hip joint function scale (HHS) between the two groups. Follow-up assessments were conducted for up to 24 months. A Student's t test was utilized for the statistical analysis. RESULTS: This study demonstrated that intra-articular TXA effectively reduced TBL (1248.19 ± 439.88 mL, p < 0.001), VBL (490.32 ± 344.34 mL, p = 0.003), and OBL (757.87 ± 381.48 mL, p = 0.004) in PWH who underwent THA. TXA demonstrated effectiveness in reducing VAS scores on POD1, POD7, and POD14 and joint swelling rates on POD1, POD7, POD14, and at discharge (p < 0.05). Additionally, the TXA group achieved higher HHS ratings at all follow-up time points (p < 0.05), showing superior hip joint mobility, lower postoperative inflammation levels, reduced factor VIII consumption during surgery, and less postoperative nutritional loss. No statistically significant differences were observed between the two groups in terms of hospital stay, hospitalization costs, surgery duration, and coagulation indicators. CONCLUSION: Intra-articular injection of TXA reduces perioperative bleeding in PWH undergoing THA while also improving joint mobility, post-operative rehabilitation, and quality of life. This may provide value for the future application of TXA in PWH.

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling.

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N=5) and osteoarthritis (OA) (N=5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

The effects of ß-hydroxy-ß-methylbutyrate or HMB-rich nutritional supplements on sarcopenia patients: a systematic review and meta-analysis.

Background: Sarcopenia is a progressive, systemic skeletal muscle disorder. Resistance exercise and physical activity have been proven effective in its treatment, but consensus on pharmacological interventions has not yet been reached in clinical practice. ß-Hydroxy-ß-methylbutyrate (HMB) is a nutritional supplement that has demonstrated favorable effects on muscle protein turnover, potentially contributing to beneficial impacts on sarcopenia. Aim: To assess the potential positive effects of HMB or HMB-containing supplements on individuals with sarcopenia, a systematic review and meta-analysis was conducted. Methods: A systematic review and meta-analysis were conducted on randomized controlled trials (RCTs) examining the treatment of sarcopenia with HMB. Two assessors independently conducted screening, data extraction, and bias risk assessment. Outcome data were synthesized through a random-effects model in meta-analysis, using the mean difference (MD) as the effect measure. Results: A meta-analysis was conducted on six studies. HMB or HMB-rich nutritional supplements showed a statistically significant difference in Hand Grip Strength (HGS) for sarcopenia patients [MD = 1.26, 95%CI (0.41, 2.21), p = 0.004], while there was no statistically significant difference in Gait Speed (GS) [MD = 0.04, 95%CI (-0.01, 0.08), p = 0.09], Fat Mass (FM) [MD = -0.18, 95%CI (-0.38, 0.01), p = 0.07], Fat-Free Mass (FFM) [MD = 0.09, 95%CI (-0.23, 0.42), p = 0.58], and Skeletal Muscle Index (SMI) [MD = 0.01, 95%CI (-0.00, 0.01), p = 0.13]. Conclusion: HMB or HMB-rich nutritional supplements are beneficial for muscle strength in sarcopenia patients. However, there is limited evidence demonstrating significant effects on both muscle strength and physical performance in sarcopenia individuals. HMB may be considered as a treatment option for sarcopenia patients. Systematic review registration: CRD42024512119.