Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) of the elderly population. Sirtuin 1 (SIRT1), as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, has been reported to participate in various aging-related signaling pathways and exert protective effect on many human diseases. SIRT1 functioned as an important role in the occurrence and progression of sarcopenia through regulating key pathways related to protein homeostasis, apoptosis, mitochondrial dysfunction, insulin resistance and autophagy in skeletal muscle, including SIRT1/Forkhead Box O (FoxO), AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor κB (NF-κB), SIRT1/p53, AMPK/SIRT1/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and SIRT1/live kinase B1 (LKB1)/AMPK pathways. However, the specific mechanisms of these processes have not been fully illuminated. Currently, several SIRT1-mediated interventions on sarcopenia have been preliminarily developed, such as SIRT1 activator polyphenolic compounds, exercising and calorie restriction. In this review, we summarized the predominant mechanisms of SIRT1 involved in sarcopenia and therapeutic modalities targeting the SIRT1 signaling pathways for the prevention and prognosis of sarcopenia.

Background: Musculoskeletal disorders cause pain, disability, and financial burdens, with rising prevalence. Virtual reality (VR) offers immersive, digital rehabilitation potential, improving motor functions and pain management. Objective: To evaluate the impact of VR on the rehabilitation of musculoskeletal disorders and to assess the consistency of evidence provided by existing systematic reviews and meta-analyses, this study focuses on musculoskeletal disorders, which encompass conditions affecting the locomotor system, such as arthritis, joint deformities, and injuries. VR therapy leverages immersive digital environments to enhance rehabilitation through digital exercises and simulations. Methods: The PubMed or MEDLINE, Embase, and Cochrane Library databases were systematically searched for relevant papers published up to April 2024. Literature screening, quality assessment, and data extraction were conducted according to predefined inclusion and exclusion criteria. The methodological quality of the included meta-analyses was evaluated using the Measurement Tool to Assess Systematic Reviews 2. The Grading of Recommendations Assessment, Development, and Evaluation system was used to classify the evidence level for each outcome as high, moderate, low, or very low. Additionally, the evidence was categorized into 5 levels based on classification criteria: I (convincing), II (highly suggestive), III (suggestive), IV (weak), and nonsignificant. Results: This umbrella review synthesized data from 14 meta-analyses published between 2019 and 2024, involving a total of 13,184 patients. In total, 7 meta-analyses received high Measurement Tool to Assess Systematic Reviews 2 ratings, 7 were rated moderate, and the remainder were rated low. VR demonstrated promising results in musculoskeletal rehabilitation, significantly reducing knee pain (mean difference [MD] –1.38, 95% CI –2.32 to –0.44; P=.004; I2=94%) and improving balance. For patients with fibromyalgia syndrome, VR effectively reduced pain (standardized mean difference [SMD] –0.45, 95% CI –0.70 to –0.20; P<.001), fatigue (SMD –0.58, 95% CI –1.01 to –0.14; P=.01), anxiety (SMD –0.50, 95% CI –0.908 to –0.029; P=.04), and depression (SMD –0.62, 95% CI –0.76 to –0.15; P=.003) while also enhancing quality of life. In individuals with back pain, VR alleviated pain-related fears (MD –5.46, 95% CI –9.40 to –1.52; P=.007; I2=90%) and reduced pain intensity (MD –1.43, 95% CI –1.86 to –1.00; P<.001; I2=95%). After arthroplasty, VR improved knee functionality (MD 8.30, 95% CI 6.92-9.67; P<.001; I2=24%) and decreased anxiety (MD –3.95, 95% CI –7.76 to –0.13; P=.04; I2=0%). Conclusions: VR demonstrates significant potential in the rehabilitation of various musculoskeletal conditions. It effectively alleviates pain, enhances psychological well-being, and facilitates the recovery of motor function in patients. Trial Registration: PROSPERO CRD42024538469; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024538469

Osteoarthritis (OA) is a major cause of disability, characterized by chronic pain, irreversible destruction, and loss of function of the articular cartilage. The integrity and arrangement of the composition and structure of the extracellular matrix (ECM) are essential for maintaining the elasticity, integrity, and mechanical support function of the cartilage tissue. Osteoarthritis causes substantial changes in the ECM, driving the progression of the disease. Recent studies have shown that the ECM plays a critical role in the development of cartilage tissue as well as the occurrence and development of osteoarthritis by directly or indirectly regulating chondrocyte proliferation, apoptosis, differentiation, and gene expression. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs derived from large transcripts. Mutations and disorders of lncRNAs are closely related to the development of osteoarthritis. Abnormal expression of lncRNAs in osteoarthritic cartilage regulates the synthesis and decomposition of the cartilaginous ECM. Therefore, the use of lncRNAs as nucleic acid drugs that regulate their targets may reduce ECM degradation, thereby delaying the pathological progression of osteoarthritis. In this review, the regulatory effects of lncRNAs on ECM in different cell behaviors related to OA are summarized. The roles of lncRNAs in the proliferation, apoptosis, differentiation, and ECM-related gene activity of chondrocytes, as well as the application of lncRNAs as potential gene therapy drugs for the repair and regeneration of osteoarthritic tissue, are also reviewed. A better understanding of the roles of lncRNAs in guiding chondrocyte behavior and ECM metabolism is critical for their future applications in osteoarthritis therapy and regenerative medicine.

Background: The objective of this review is to evaluate the methodological quality of meta-analyses and observe the consistency of the evidence they generated to provide comprehensive and reliable evidence for the clinical use of three-dimensional (3D) printing in surgical treatment of fracture. Methods: We searched three databases (PubMed, Embase, and Web of Science) up until August 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were adhered to in this review. The Measurement Tool to Assess Systematic Reviews (AMSTAR) 2 was used to rate the quality and reliability of the meta-analyses (MAs), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to grade the outcomes. Furthermore, Graphical Representation of Overlap for Overviews (GROOVE) was employed to examine overlap, and the resulting evidence was categorized into four groups according to established criteria for evidence classification. Results: Results from 14 meta-analyses were combined. AMSTAR 2 gave six meta-analyses a high rating, six MAs a moderate rating, and two MAs a low rating. Three-dimensional printing shows promising results in fracture surgical treatment, significantly reducing operation time and loss of blood for tibial plateau fracture. For acetabular fracture, apart from the positive effects on operation time (ratio of mean (ROM) = 0.74, 95% confidence interval (CI), 0.66–0.83, I ² = 93%) and blood loss (ROM = 0.71, 95% CI 0.63–0.81, I ² = 71%), 3D printing helps reduce postoperative complications (odds ratio (OR) = 0.42, 95% CI, 0.22–0.78, I ² = 9%). For proximal humerus fracture, 3D printing helps shorten operation time (weighted mean difference (WMD) = −19.49; 95% CI −26.95 to −12.03; p < 0.05; I ² = 91%), reduce blood loss (WMD = −46.49; 95% CI -76.01 to −16.97; p < 0.05; I ² = 98%), and get higher Neer score that includes evaluation of pain, function, range of motion, and anatomical positioning (WMD = 9.57; 95% CI 8.11 to 11.04; p < 0.05; I ² = 64%). Additionally, positive results are also indicated for other fractures, especially for operation time, blood loss, and postoperative complications. Conclusions: Compared with traditional fracture surgical treatment, 3D-printing-assisted surgery has significant advantages and great effectiveness in terms of operation time, loss of blood, and postoperative complications in the treatment of many different types of fractures, with less harm to patients.

Objective: The aim of the study was to evaluate the efficacy and safety of teriparatide compared to other treatments for postmenopausal osteoporosis. Methods: A review of studies from 2000 to January 2023 analyzed randomized controlled trials on postmenopausal women treated with teriparatide (PTH 1–34), comparing it to placebo or other osteoporosis treatments. The analysis focused on bone mineral density (BMD), bone turnover markers, and clinical outcomes, employing Review Manager 5.4.1 and the RoB 2 tool for bias assessment. Results: Our analysis of 23 randomized controlled trials (RCTs) found that PTH (134) treatment significantly increased lumbar spine BMD (mean difference (MD) = 0.02, 95% CI: 0.01–0.03) and femoral neck BMD (MD = 0.01, 95% CI: 0.00–0.01). However, there were no significant changes in total hip and radial bone BMD among the 3536 and 2046 participants, respectively. We also found that PTH (1–34) increased P1NP in a larger cohort (n = 1415) when compared to osteocalcin (n = 206). Although the risk of adverse events increased (relative risk (RR) = 1.65, 95% CI: 1.32–2.07), the incidence of fractures decreased significantly (RR = 0.57, 95% CI: 0.45–0.072), with no significant difference observed in mortality rates between treatment and control groups. Conclusion: Teriparatide improves lumbar spine and femoral neck BMD in postmenopausal women. Particularly notable is the novel finding regarding its effect on radius BMD, an area less explored in previous research. Despite an uptick in adverse events, the marked decrease in fracture incidence confirms its clinical utility for high-risk osteoporosis patients, highlighting the necessity for ongoing investigations into its full skeletal effects.

Background: The purpose of this study was to determine the role of Orai1 in the regulation of the proliferation and cell cycle of osteoblasts. Methods: The expression of Orai1 was inhibited by Orai1 small interfering RNA (siRNA) in MC3T3-E1 cells. Following Orai1 downregulation, cell proliferation and cell cycle were examined. Furthermore, the expression of cyclin D1, cyclin E, CDK4, and CDK6 was analyzed. The activity of the Ras-NF-κB signaling pathway was investigated to identify the role of Orai1 in the regulation of osteoblast proliferation. Results: Orai1 was successfully downregulated in MC3T3-E1 cells by the Orai1 siRNA transfection (p < 0.05). We found that MC3T3-E1 cell proliferation was decreased, and the cell cycle was arrested by Orai1 downregulation (p < 0.05). Additionally, the expression of cyclin D1 was decreased by Orai1 downregulation (p < 0.05), as was the activity of the Ras-NF-κB signaling pathway (p < 0.05). Orai1 siRNA did not further reduce cell proliferation, the proportion of cells in the S phase, and cyclin D1 expression after chemical blockage of the Ras signaling pathway in MC3T3-E1 cells (p > 0.05). Conclusions: The results reveal that Orai1 downregulation may reduce cyclin D1 expression by inactivating the Ras-NF-κB signaling pathway thus blocking osteoblast proliferation and cell cycle.