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Introduction: Research has highlighted the role of runt-related transcription factor 2 (Runx2) in the development of osteoarthritis (OA); however, its causal association remains unclear. This study aimed to explore whether Runx2 expression is causally associated with OA and assess its therapeutic potential for OA. Methods: Genetic proxy instruments for Runx2 expression were obtained from gene expression quantitative trait locus (eQTLs) study of eQTLGen Consortium (n = 31,684). Aggregated genome-wide association study (GWAS) data for OA (including all OA [177,517 cases and 649,173 controls], knee OA (KOA) [62,497 cases and 333,557 controls], and hip OA (HOA) [36,445 cases and 316,943 controls]) were extracted from the Genetics of Osteoarthritis Consortium. We integrated eQTLs data with OA GWAS data to estimate their causal association and to estimate the potential of Runx2 as a drug target in the treatment of OA using summary data-based Mendelian randomization (SMR) analysis. Furthermore, different OA GWAS data (including all OA [77,052 cases and 378,169 controls], KOA [24,955 cases and 378,169 controls], and HOA [15,704 cases and 378,169 controls]) derived from the GWAS Catalog database were used for replication study. Results: SMR analysis showed that high expression levels of Runx2 were associated with an increased risk of all OA [odds ratio (OR) 1.044, 95% confidence interval (CI) 1.023–1.067; P = 5.03 × 10−5], KOA (OR 1.040, 95% CI 1.006–1.075; P = 0.021), and HOA (OR 1.067, 95% CI 1.022–1.113; P = 0.003). This suggests that Runx2 inhibitors may have promising potential for the treatment of OA. Notably, the causal effects of Runx2 with all OA (OR 1.053, 95% CI 1.027–1.079; P = 3.95 × 10−5) and KOA (OR 1.043, 95% CI 1.001–1.087; P = 0.045) were repeated in the replication study, but limited evidence supported the association of Runx2 expression levels with HOA (OR 1.045, 95% CI 0.993–1.101; P = 0.094). Conclusions: Our analyses indicate a positive correlation between Runx2 expression and OA risk across all three phenotypes, suggesting the potential of Runx2 inhibitors in the treatment of OA and providing evidence from a genetic perspective. [ABSTRACT FROM AUTHOR]

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the organism. Among its various forms, skeletal interoception specifically regulates the metabolic homeostasis of bones. Osteoarthritis (OA) is a complex joint disorder involving cartilage, subchondral bone, and synovium. The subchondral bone undergoes continuous remodeling to adapt to dynamic joint loads. Recent findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone, resulting in subchondral bone sclerosis in OA. The skeletal interoception is also a potential mechanism for chronic synovial inflammation in OA. In this review, we offer a general overview of interoception, specifically skeletal interoception, subchondral bone microenviroment and the aberrant subchondral remedeling. We also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA, as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception. [ABSTRACT FROM AUTHOR]

Background: To compare the gait patterns between posterior cruciate retention and substitution in total knee arthroplasty (TKA). Methods: Electronic databases including the PubMed, Embase, CINAHL, Web of Science, and Cochrane databases were searched to identify clinical trials investigating posterior cruciate retention versus substitution in TKA. The outcome measurements were the kinematic gait parameters (flexion at heel strike, maximum flexion during loading response, flexion range during loading, minimal flexion at terminal stance, maximal flexion at the swing, and total flexion during the gait cycle), Knee Society Score (KSS), knee flexion, knee extension, and walking speed. Statistical software Review Manager 5.4 and Stata 14.0 were used for data analysis. Results: There were finally 9 studies included in this meta-analysis. The results did not reveal differences between posterior cruciate retention (CR) and posterior cruciate substitution (PS) groups in TKA, in terms of kinematic gait parameters, knee extension, walking speed, and KSS. However, the PS group had a significantly larger knee flexion angle than that in the CR group [weighted mean difference = − 3.20, 95% CI − 6.13 to − 0.28, P = 0.03]. Conclusion: Both the posterior cruciate retention and posterior cruciate substitution lead to obvious improvements in patient function and have their advantages in getting a good cup position. The PS design is significantly better on the knee flexion, while there are no statistical differences in kinematic gait parameters and outcome scores between them. This might indicate that surgeons do not necessarily need a PS design to substitute the posterior cruciate ligament during TKA. [ABSTRACT FROM AUTHOR]

Harmful algae blooms have expanded greatly in recent decades, and their secreted toxins pose a severe threat to human health and marine ecosystems. Saxitoxin (STX) is a main paralytic shellfish poison naturally produced by marine microalgae of the genus Alexandrium. Despite numerous studies have assessed the impacts of STX on marine bivalves, comparative in vivo study on the toxicity of STX on bivalves with distinct accumulation ability (such as oysters and scallops) has been seldom investigated. The aim of this study was to identify whether distinct sensitivity exists between oysters, Crassostrea gigas , and scallops, Chlamys farreri under the same amount of STX exposure using multiple biomarker responses. The responses of different biochemical markers including oxidative stress markers (catalase, superoxide dismutase, glutathione S -transferase, and lipid peroxidation) and immunotoxicity biomarkers (hemocyte phagocytosis rate, reactive oxidative species production, and DNA damages) were evaluated in bivalves after 12, 48, and 96 h of exposure to STX. The integrated biomarker responses value combined with two-way ANOVA analysis suggested that STX posed slightly severer stress on scallops than oysters for the extended period of time. This study provided preliminary results on the usefulness of a multi-biomarker approach to assess the toxicity associated with STX exposure in marine bivalves. [ABSTRACT FROM AUTHOR]

Negative physiological impacts induced by exposure to acidified seawater might sensitize marine organisms to future environmental stressors, such as disease outbreak. The goal of this study was to evaluate if ocean acidification (OA) could reduce the resistance capability of the Pacific oyster (Crassostrea gigas) to Vibrio splendidus challenge from an energy metabolism perspective. In this study, the Pacific oyster was exposed to OA (pH 7.6) for 28 days and then challenged by V. splendidus for another 72 h. Antioxidative responses, lipid peroxidation, metabolic (energy sensors, aerobic metabolism, and anaerobic metabolism) gene expression, glycolytic enzyme activity, and the content of energy reserves (glycogen and protein) were investigated to evaluate the environmental risk of pathogen infection under the condition of OA. Our results demonstrated that following the exposure to seawater acidification, oysters exhibited an energy modulation with slight inhibition of aerobic energy metabolism, stimulation of anaerobic metabolism, and increased glycolytic enzyme activity. However, the energy modulation ability and antioxidative regulation of oysters exposed to seawater acidification may be overwhelmed by a subsequent pathogen challenge, resulting in increased oxidative damage, decreased aerobic metabolism, stimulated anaerobic metabolism, and decreased energy reserves. Overall, although anaerobic metabolism was initiated to partially compensate for inhibited aerobic energy metabolism, increased oxidative damage combined with depleted energy reserves suggested that oysters were in an unsustainable bioenergetic state and were thereby incapable of supporting long-term population viability under conditions of seawater acidification and a pathogen challenge from V. splendidus. [ABSTRACT FROM AUTHOR]

Persistent organic pollutants (POPs) are ubiquitous and coexisted in the aquatic environment. Individual and combined toxic effects of benzo[a]pyrene (BaP) and 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) on embryogenesis, and larval survival of the Pacific oyster were investigated. The EC values of BaP, BDE-47 and their mixture on embryogenesis were 18.4, 203.3 and 72.0 µg/L respectively, while the LC values for 96 h larval mortality were 26.8, 244.5 and 108.9 µg/L respectively. The Marking-Dawson additive toxicity indices were −0.02 and −0.19, indicating an additive effect with a trend to antagonism. In addition, DNA strand breaks were also observed in oyster embryos after exposure. Our study suggests that BaP and BDE-47 exposure can cause developmental abnormalities, DNA damage and larval mortality. Furthermore, the toxicity of the mixture is slightly lower than individual pollutant. These data will be helpful to predict the toxicity of organic pollutants, and provide criteria for marine water quality standards. [ABSTRACT FROM AUTHOR]