O-linked ß-N-acetylglucosaminylation may be a key regulatory factor in promoting osteogenic differentiation of bone marrow mesenchymal stromal cells.

Cumulative evidence suggests that O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) plays an important regulatory role in pathophysiological processes. Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated, the potential mechanisms of O-GlcNAcylation in bone metabolism, particularly, in the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) remains unexplored. In this study, the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed, assuming that it could trigger more scholars to focus on research related to O-GlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis.

Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis.

BACKGROUND: Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation. AIM: To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms. METHODS: 20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation. RESULTS: Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence. CONCLUSION: Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.

Evaluation of Quantitative and Selective Sensory Fiber Dysfunction in Patients with Cirrhosis.

BACKGROUND: Chronic liver disease has been reported to be associated with peripheral neuropathy. However, which sensory fibers are affected remains unknown. The objective of this study was to examine the function of sensory nerve fibers in patients with cirrhosis using the current perception threshold (CPT) test, as well as the correlation between blood biochemical indicators related to cirrhosis and CPT values. METHODS: We recruited 44 patients with liver cirrhosis and 37 healthy controls of the same age and gender. The Neurometer® system for the CPT test was used to stimulate the median nerve on the right index finger, as well as the deep and superficial peroneal nerves on the right hallux, using three distinct parameters (2000 Hz, 250 Hz, and 5 Hz). Comparative analysis was performed on the CPT values of the sensory nerves. Additionally, the correlation between CPT values and biochemical blood indicators in the study participants was analyzed. RESULTS: Under 2000 Hz electrical stimulation, there was a significant difference between the cirrhosis and healthy control groups in the median nerve as well as the deep and superficial peroneal nerves (p < 0.05). In addition, the median nerve CPT value of the cirrhosis group was significantly higher than that of the control group at an electrical stimulation frequency of 250 Hz (p = 0.005). There was no correlation between CPT values and blood biochemical indicators. CONCLUSION: According to the results, the sensory peripheral neuropathy in liver cirrhosis is mainly manifested as Aß fiber neuropathy.

Nuclear magnetic resonance-based metabolomic study of rat serum after anterior cruciate ligament injury.

Anterior cruciate ligament (ACL) injury, a common sports injury, is associated with a high risk of subsequent osteoarthritis (OA), which can cause serious pain and disability. Understanding the detailed mechanism underlying the predisposition of knee with ACL injury to secondary OA at an early stage is key to preventing future degradation and progression to a clinically significant disease. A total of 56 male Sprague Dawley rats (age, 8 weeks; weight, 180-220 g) were randomly divided into three experimental groups: control, ACL transection (ACLT; where surgical procedure was performed with ACLT), and sham (where surgical procedure was performed without ACLT). The ACLT and sham groups were further divided into three subgroups based on when the rats were sacrificed: 4, 8, and 12 weeks after the surgical procedure. The control group and the aforementioned subgroups contained 8 rats each. We used nuclear magnetic resonance (NMR)-based metabolomic analysis to analyze rat serum samples for the metabolic characteristics and the underlying mechanisms. In total, 28 metabolites were identified in the NMR spectra of the rat sera. At 4 and 8 weeks postoperatively, the sham group demonstrated metabolic profiles different from those of the ACLT group. However, this difference was not observed 12 weeks postoperatively. In total, five metabolites (acetate, succinate, sn-glycero-3-phosphocholine, glucose, and phenylalanine) and five metabolic pathways (phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; pyruvate metabolism; starch and sucrose metabolism; and histidine metabolism) demonstrated significant differences between the ACLT and sham groups. ACL injury was noted to considerably affect biochemical homeostasis and metabolism; however, these metabolic changes persisted briefly. Moreover, glucose was a characteristic metabolite, and several energy-related metabolic pathways were significantly disturbed. Therefore, an ACL injury may lead to considerable impairments in energy metabolism. Abnormal glucose levels facilitate chondrocyte function impairment and thereby lead to OA progression. Furthermore, lactate may aid in identifying metabolic changes specific to knee trauma not related to an ACL injury. Overall, the metabolic changes in rat serum after an ACL injury were closely related to disturbances in energy metabolism and amino acid metabolism. The current results may aid in understanding the pathogenesis of posttraumatic osteoarthritis.

Short-term efficacy of repetitive transcranial magnetic stimulation in SCA3: A prospective, randomized, double-blind, sham-controlled study.

OBJECTIVE: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia globally. No effective treatment is currently available for SCA3. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive form of brain stimulation, demonstrated to improve symptoms in patients with neurodegenerative cerebellar ataxias. The present study investigated whether treatment with rTMS over the cerebellum for 15 consecutive days improved measures of ataxia in SCA3 patients. METHODS: A double-blind, prospective, randomized, sham-controlled trial was carried out on 44 SCA3 patients. Participants were randomly assigned to two groups: real or sham stimulation. Each participant underwent 30 minutes of 1Hz rTMS stimulation (a total of 900 pulses) for 15 consecutive days. The primary outcome measure was the score on the International Cooperative Ataxia Rating Scale (ICARS), and secondary outcomes were from the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). RESULTS: Nausea was the only adverse effect reported by 2 participants from the sham and real group. After 15 days of treatment, there was a significant improvement in all performance scores in both real and sham stimulation groups. However, compared to the sham group, the improvements were significantly larger in the real group for the ICARS (P = 0.002), SARA (P = 0.001), and BBS (P = 0.001). INTERPRETATION: A 15 days treatment with rTMS over the cerebellum improves the symptoms of ataxia in SCA3 patients. Our results suggest that rTMS is a promising tool for future rehabilitative approaches in SCA3.

Advances in Stem Cell Therapies for Rotator Cuff Injuries.

Rotator cuff injury is a common upper extremity musculoskeletal disease that may lead to persistent pain and functional impairment. Despite the clinical outcomes of the surgical procedures being satisfactory, the repair of the rotator cuff remains problematic, such as through failure of healing, adhesion formation, and fatty infiltration. Stem cells have high proliferation, strong paracrine action, and multiple differentiation potential, which promote tendon remodeling and fibrocartilage formation and increase biomechanical strength. Additionally, stem cell-derived extracellular vesicles (EVs) can increase collagen synthesis and inhibit inflammation and adhesion formation by carrying regulatory proteins and microRNAs. Therefore, stem cell-based therapy is a promising therapeutic strategy that has great potential for rotator cuff healing. In this review, we summarize the advances of stem cells and stem cell-derived EVs in rotator cuff repair and highlight the underlying mechanism of stem cells and stem cell-derived EVs and biomaterial delivery systems. Future studies need to explore stem cell therapy in combination with cellular factors, gene therapy, and novel biomaterial delivery systems.

Quantitative and Fiber-Selective Evaluation for Central Poststroke Pain.

The electrophysiological recording can be used to quantify the clinical features of central poststroke pain (CPSP) caused by different lesion locations. We aimed to explore the relationship between clinical features and lesion location in patients with CPSP using the current perception threshold (CPT) approach. Here, patients underwent the standardized CPT measure at five detection sites on both the contralesional and ipsilesional sides, using a constant alternating-current sinusoid waveform stimulus at three frequencies: 2000 Hz, 250 Hz, and 5 Hz. 57 CPSP patients were recruited in this cross-sectional study, including 13 patients with thalamic lesions and 44 patients with internal capsule lesions. Patients with a thalamic lesion had more frequent abnormal Aδ and C fibers than those with an internal capsule lesion (69.2% versus 36.4%, p value = 0.038; 53.8% versus 63.6%, p value = 0.038). The patients with internal capsule lesions had more frequent abnormal Aß fibers than those with thalamic lesions (53.8% versus 63.6%, p value < 0.001). The sensory dysfunction in the patients with thalamic lesions was more likely to occur in the upper limbs (i.e., the shoulder (p value = 0.027) and the finger (p value = 0.040)). The lower limbs (i.e., the knee (p value = 0.040) and the toe (p value = 0.005)) were more likely to experience sensory dysfunction in the patients with internal capsule lesions. Hyperesthesia was more likely to occur in the thalamic patients, and hypoesthesia was more likely to occur in the patients with internal capsule lesions (p value < 0.001). In patients with thalamic lesions, Visual Analogue Scale (VAS) had a positive correlation with 5 Hz CPT on the shoulder (r = 0.010, p value = 0.005), 250 Hz CPT on the finger (r = 0.690, p value = 0.009) from the contralesional side, and 2000 Hz CPT on the knee (r = 0.690, p value = 0.009). In patients with internal capsule lesions, VAS had a positive correlation with 2000 Hz CPT on the knee (r = 0.312, p value = 0.039) and foot (r = 0.538, p value < 0.001). In conclusion, the abnormal fiber types, sensory dysfunction territory, and clinical signs of CPSP in thalamic stroke differ from those in internal capsule stroke. Implementation of the portable and convenient CPT protocol may help clarify the locations of different stroke lesions in various clinical settings.

Effect of Exercise on the Cognitive Function of Older Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: Aging and type 2 diabetes mellitus (T2DM) are important risk factors for the development of cognitive deterioration and dementia. The objective of this research was to investigate the effects of an exercise intervention on cognitive function in older T2DM patients. Methods: Eight literature databases (PubMed, EBSCO, Scopus, Embase, The Cochrane Library, Web of Science, Ovid, and ProQuest) were searched from inception to 20 January 2022. The researchers examined randomized controlled trials (RCTs) that evaluated the impact of exercise on the cognitive performance of older T2DM patients. The Cochrane risk-of-bias tool (ROB 2) for RCTs was used to assess each study. The quality of evidence was assessed using the GRADE (grading of recommendations, assessment, development, and evaluations) approach. The mini-mental state examination (MMSE), Modified MMSE (3MSE), and Montreal cognitive assessment (MoCA) were used to evaluate the cognitive outcomes. We performed a subgroup analysis with stratification according to exercise intervention modality, duration, and cognitive impairment. Results: Five trials were eligible, with a total of 738 T2DM patients. The combined findings revealed that exercise improved global cognitive function significantly (standardized mean difference: 1.34, 95% confidence interval: 0.23-2.44, p < 0.01). The effect of exercise on global cognitive performance was not significantly influenced by intervention modality, intervention duration, or cognitive impairment in the sub-group analysis (p > 0.05). In the studies that were included, no relevant adverse events were reported. Conclusion: Exercise is beneficial in improving global cognitive function in older adults with T2DM. Studies with bigger sample sizes and higher quality are additionally expected to draw more definite conclusions. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42022296049].

Depression in Osteoarthritis: Current Understanding.

Depression, one of the most common comorbidities with osteoarthritis (OA), affects patient prognosis and quality of life. It also increases the overall burden of disease. This subgroup of patients has not been effectively managed in clinical settings. The study aimed to direct physicians' attention to the co-occurrence of depression and OA. Therefore, this review summarizes the relevant literature published over the past 10 years. The focus is on the prevalence of and risk factors for depression in OA, the effects of depression on OA development and treatment response, comorbidity mechanisms, screening, and non-pharmacological treatment. The research on the etiology of depression has been driven largely by epidemiological studies. Recent studies have shown that high levels of pain, poor levels of function, high numbers of OA sites, and slow gait might be associated with depression. However, the pathophysiology of OA and depression comorbidities remains unclear. In addition to immune inflammation and structural changes in the brain, which have been documented in brain imaging studies, psychosocial factors may also play a role. The evidence indicates that depression can be treated with early intervention; however, adjustments may need to be made for individuals with comorbid depression in OA. It is recommended that health care providers pay more attention to depressive symptoms in patients with OA. Clinicians should develop and implement an individualized and comprehensive treatment plan for patients based on a mental health assessment and in teams with other professionals to optimize treatment outcomes.

Effect of low-load resistance training with different degrees of blood flow restriction in patients with knee osteoarthritis: study protocol for a randomized trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative disease that causes pain, functional impairment, and reduced quality of life. Resistance training is considered as an effective approach to reduce the risk of muscle weakness in patients with KOA. Blood flow restriction (BFR) with low-load resistance training has better clinical outcomes than low-load resistance training alone. However, the degree of BFR which works more effectively with low-load resistance training has not been determined. The purpose of this study is to evaluate the effectiveness of different degrees of BFR with low-load resistance training in patients with KOA on pain, self-reported function, physical function performance, muscle strength, muscle thickness, and quality of life. METHODS: This is a study protocol for a randomized, controlled trial with blinded participants. One hundred individuals will be indiscriminately assigned into the following groups: two training groups with a BFR at 40% and 80% limb occlusion pressure (LOP), a training group without BFR, and a health education group. The three intervention groups will perform strength training for the quadriceps muscles twice a week for 12 weeks, while the health education group will attend sessions once a week for 12 weeks. The primary outcome is pain. The secondary outcomes include self-reported function, physical function performance, muscle strength of the knee extensors, muscle mass of the quadriceps, quality of life, and adverse events. Intention-to-treat analysis will be conducted for individuals who withdraw during the trial. DISCUSSION: Previous studies have shown that BFR with low-load resistance training is more effective than low-load resistance training alone; however, a high degree of BFR may cause discomfort during training. If a 40% LOP for BFR could produce similar clinical outcomes as an 80% LOP for BFR, resistance training with a low degree of BFR can be chosen for patients with KOA who are unbearable for a high degree of BFR. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000037859 ( http://www.chictr.org.cn/edit.aspx?pid=59956&htm=4 ). Registered on 2 September 2020.

Efficacy and Safety of Blood Flow Restriction Training in Patients With Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of blood flow restriction training (BFRT) in the treatment of patients with knee osteoarthritis (OA). METHOD: Seven electronic databases were searched to identify trials comparing BFRT and conventional resistance training in a population with knee OA. Studies were selected according to the inclusion and exclusion criteria. Standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated to compare outcome measures of the groups. The methodologic quality of selected studies and the quality of evidence were evaluated for included studies. RESULTS: A total of 5 studies were included in this meta-analysis, with very low to moderate risk of bias. The pooled results showed no significant difference between BFRT and conventional resistance training for knee OA, including pain (SMD -0.04 [95% CI -0.31, 0.24], P = 0.79), physical function performance (SMD 0.12 [95% CI -0.55, 0.78], P = 0.73), self-reported function (SMD 0.14 [95% CI -0.24, 0.52], P = 0.48), and adverse events (RR 0.45 [95% CI 0.20, 1.01], P = 0.05). In subgroup analysis, BFRT had a lower incidence of adverse events when compared with high-load resistance training (HLRT). CONCLUSION: Data from pooled studies showed that BFRT may not have greater efficacy for treating patients with knee OA, and it is less likely to have a higher risk of adverse events. However, limited evidence supports the idea that BFRT is likely safer than HLRT. More evidence with high quality is needed in further research on efficacy and safety.

Stem cell therapies in tendon-bone healing.

Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.

Factors associated with public attitudes towards persons with disabilities: a systematic review.

OBJECTIVE: The aim of this review is to identify and summarize factors that are associated with public attitudes towards people with various disabilities systematically. METHODS: An electronic search of three databases was performed (Medline, EMBASE and Cochrane) covering the period from 1950 to present. A comprehensive search strategy was developed and the lists of citations were screened for potential eligible studies. Only quantitative studies using valid measurements were included, and the methodological quality of included studies was appraised based on three criteria (sample, measurement, analysis) by two independent reviewers. RESULTS: The initial electronic search yielded 995 articles after duplicates removed, and 27 studies met the eligibility criteria were included in the study. Three categories of the factors were found to be associated with the public attitudes, which are related to the attitude provider, disabled people, and society respectively. Specifically, the more people know about disabilities, the more likely they were to have positive attitude; and the frequency and quality of the contact with the disabled are also proved to be influential to the attitudes. Meanwhile, the type of disability is also closely correlated to the public's attitude towards the disabilities. CONCLUSION: People's knowledge of the disability and their contact with individuals with disabilities are the main influential factors in public attitudes towards persons with disabilities.

Excessive mechanical stretch­mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/ß­catenin signaling pathway.

Excessive biomechanical loading is considered an important cause of osteoarthritis. Although the mechanical responses of chondrocytes and osteoblasts have been investigated, their communication during mechanical loading and the underlying molecular mechanisms are not yet fully known. The present study investigated the effects of excessive mechanically stretched osteoblasts on the metabolism and apoptosis of chondrocytes, and also assessed the involvement of the Wnt/ß­catenin signaling pathway. In the present study, rat chondrocytes and osteoblasts were subjected to mechanical tensile strain, and an indirect chondrocyte­osteoblast co­culture model was established. Reverse transcription­quantitative PCR and western blotting were performed to determine the expression levels of genes and proteins of interest. An ELISA was performed to investigate the levels of cytokines, including matrix metalloproteinase (MMP) 13, MMP 3, interleukin­6 (IL­6) and prostaglandin E2 (PG E2), released from osteoblasts. Flow cytometry was performed to detect the apoptosis of chondrocytes exposed to stretched osteoblast conditioned culture medium. The levels of MMP 13, IL­6 and PG E2 increased significantly in the supernatants of stretched osteoblasts compared with the un­stretched group. By contrast, the mRNA expression levels of Collagen 1a and alkaline phosphatase were significantly decreased in osteoblasts subjected to mechanical stretch compared with the un­stretched group. The mRNA expression level of Collagen 2a was significantly decreased, whereas the expression levels of MMP 13 and a disintegrin and metalloproteinase with thrombospondin­like motifs 5 were significantly increased in chondrocytes subjected to mechanical stretch compared with the un­stretched group. In the co­culture model, the results indicated that excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes, which was partly inhibited by Wnt inhibitor XAV­939. The results of the present study demonstrated that excessive mechanical stretch led to chondrocyte degradation and inhibited osteoblast osteogenic differentiation; furthermore, excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes via the Wnt/ß­catenin signaling pathway.

Is it time to put traditional cold therapy in rehabilitation of soft-tissue injuries out to pasture?

Cold therapy has been used regularly as an immediate treatment to induce analgesia following acute soft-tissue injuries, however, a prolonged ice application has proved to delay the start of the healing and lengthen the recovery process. Hyperbaric gaseous cryotherapy, also known as neurocryostimulation, has shown the ability to overcome most of the limitations of traditional cold therapy, and meanwhile promotes the analgesic and anti-inflammatory effects well, but the current existing studies have shown conflicting results on its effects. Traditional cold therapy still has beneficial effect especially when injuries are severe and swelling is the limiting factor for recovery after soft-tissue injuries, and therefore no need to be entirely put out to pasture in the rehabilitation practice. Strong randomized controlled trials with good methodological quality are still needed in the future to evaluate the effects of different cryotherapy modalities.

Treadmill running induces remodeling of the infrapatellar fat pad in an intensity-dependent manner.

OBJECTIVE: To investigate the response of the infrapatellar fat pad (IFP) to running at different intensities and further explore the underlying mechanisms of these responses under different running-induced loadings. METHODS: Animals were randomly assigned into the sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. The rats in the LIR, MIR, and HIR groups were subjected to an 8-week treadmill running protocol. In each group, the IFP was examined at the baseline and at the 8th week to perform histomorphology, immunohistochemistry, and mRNA expression analyses. RESULTS: Compared with LIR and MIR, HIR for 8 weeks led to a substantial increase in the surface cellularity (1.67 ± 1.15), fibrosis (1.29 ± 0.36), and vascularity (33.31 ± 8.43) of the IFP but did not increase IFP inflammation or M1 macrophage polarization. Low-to-medium-intensity running resulted in unchanged or decreased fibrosis, vascularity, and surface cellularity in the IFP compared to those of the SED group. Furthermore, serum leptin and visfatin levels were significantly lower in the LIR and MIR groups than in the SED group or the HIR group (P < 0.05). CONCLUSION: The effect of running on IFP remodeling was intensity dependent. In contrast to LIR and MIR, HIR increased the fibrosis and vascularity of the IFP. HIR-induced IFP fibrosis was probably due to mechanical stress, rather than pathological proinflammatory M1/M2 polarization.

Efficacy and safety of sprifermin injection for knee osteoarthritis treatment: a meta-analysis.

OBJECTIVE: To perform a meta-analysis comparing the structural progression and clinical symptom outcomes as well as adverse events experienced from intra-articular injections of sprifermin compared to a placebo treatment for patients with knee osteoarthritis (KOA). METHOD: We systematically searched the literature for studies that compared long-term outcomes between sprifermin and placebo injections for KOA treatment. Meta-analysis was performed with RevMan5.3 using an inverse variance approach with fixed or random effects models. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: Eight studies were included. Overall, there was significantly less improvement of WOMAC total scores in patients receiving sprifermin, compared with the placebo (mean difference (MD) = 3.23, 95% CI 0.76-5.69; I2 = 0%; P = 0.01). Further, sprifermin injection patients gained more, and lost less, cartilage thickness and volume in total femorotibial joint (cartilage thickness: standardized mean differences (SMD) = 0.55, 95% CI 0.26-0.84; I2 = 78%; P = 0.0002; cartilage volume: SMD = 0.39, 95% CI 0.20-0.58; I2 = 49%; P < 0.0001). Changes in the cartilage surface morphology of the medial tibio-femoral joint (MD = -0.30, 95% CI -0.44 to -0.16; I2 = 0%; P < 0.0001) and patello-femoral joint (MD = -0.22; 95% CI -0.37 to -0.07; I2 = 0%; P = 0.004) showed a significant difference between the sprifermin and placebo injections. Moreover, there were no significant differences between sprifermin and the placebo in the risk of treatment-emergent adverse events (OR = 1.05; 95% CI 0.52-2.14; I2 = 48%; P = 0.89). CONCLUSION: The data from the included studies provide strong evidence to determine the effect of intra-articular sprifermin on joint structure in individuals with KOA and show no specific adverse effects. Nevertheless, intra-articular sprifermin did not likely have any positive effect on symptom alleviation.

A review of applications of metabolomics in osteoarthritis.

Osteoarthritis (OA) represents the most prevalent and disabling arthritis worldwide due to its heterogeneous and progressive articular degradation. However, effective and timely diagnosis and fundamental treatment for this disorder are lacking. Metabolomics, a growing field in life science research in recent years, has the potential to detect many metabolites and thus explains the underlying pathophysiological processes. Hence, new specific metabolic markers and related metabolic pathways can be identified for OA. In this review, we aimed to provide an overview of studies related to the metabolomics of OA in animal models and humans to describe the metabolic changes and related pathways for OA. The present metabolomics studies reveal that the pathogenesis of OA may be significantly related to perturbations of amino acid metabolism. These altered amino acids (e.g., branched-chain amino acids, arginine, and alanine), as well as phospholipids, were identified as potential biomarkers to distinguish patients with OA from healthy individuals.

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy.

Cardiac hypertrophy is the result of increased myocardial cell size responding to an increased workload and developmental signals. These extrinsic and intrinsic stimuli as key drivers of cardiac hypertrophy have spurred efforts to target their associated signaling pathways. The extracellular signal-regulated kinases 1/2 (ERK1/2), as an essential member of mitogen-activated protein kinases (MAPKs), has been widely recognized for promoting cardiac growth. Several modified transgenic mouse models have been generated through either affecting the upstream kinase to change ERK1/2 activity, manipulating the direct role of ERK1/2 in the heart, or targeting phosphatases or MAPK scaffold proteins to alter total ERK1/2 activity in response to an increased workload. Using these models, both regulation of the upstream events and modulation of each isoform and indirect effector could provide important insights into how ERK1/2 modulates cardiomyocyte biology. Furthermore, a plethora of compounds, inhibitors, and regulators have emerged in consideration of ERK, or its MAPK kinases, are possible therapeutic targets against cardiac hypertrophic diseases. Herein, is a review of the available evidence regarding the exact role of ERK1/2 in regulating cardiac hypertrophy and a discussion of pharmacological strategy for treatment of cardiac hypertrophy.