Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest possible mechanisms thought to be responsible for PTOA, evaluate current diagnostic methods for detecting early OA, and discuss potential interventions to combat PTOA. We also identify important directions for future research. Although much work has been done, the incidence of PTOA among patients with a history of ACL injury remains high due to the complexity of ACL injury progression to PTOA, the lack of sensitive and easily accessible diagnostic methods to detect OA development, and the limitations of current treatments. A number of factors are thought to be involved in the underlying mechanism, including structural factors, biological factors, mechanical factors, and neuromuscular factor. Since there is a clear “start point” for PTOA, early detection and intervention is of great importance. Currently, imaging modalities and specific biomarkers allow early detection of PTOA. However, none of them is both sensitive and easily accessible. After ACL injury, many patients undergo surgical reconstruction of ACL to restore joint stability and prevent excessive loading. However, convincing evidence is still lacking for the superiority of ACL-R to conservative management in term of the incidence of PTOA. As for non-surgical treatment such as anti-cytokine and chemokine interventions, most of them are investigated in animal studies and have not been applied to humans. A complete understanding of mechanisms to stratify the patients into different subgroups on the basis of risk factors is critical. And the improvement of standardized and quantitative assessment techniques is necessary to guide intervention. Moreover, treatments targeted toward different pathogenic pathways may be crucial to the management of PTOA in the future.

Osteoarthritis is the most prevalent arthritis typically characterized by degradation of cartilage. However, its pathogenesis is not fully understood. Currently, osteoarthritis is best considered a disease of the whole "joint organ". Infrapatellar fat pad (IFP), an adipose tissue near synovium, is now attaching importance to researchers for its inflammatory phenotype. In this narrative review, a large body of evidence has been gathered for the involvement of IFP in the development of knee osteoarthritis. Additionally, the underlying mechanisms of how IFP can be involved in this process have been proposed. However, further investigations are needed to better understand its precise role in this process and its underlying mechanism, and beyond that, to develop new strategies to slow down the degenerative process and explore an effective and timely diagnosis of the disease.

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.

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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 MAPKKs, 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.

Purpose: In this study, we investigated the effect of treadmill exercise training on cardiac hypertrophy, collagen deposition, echo parameters and serum levels of cardiac troponin I (cTnI) in rats, and how they differ with various exercise intensities, hence exploring potential signal transduction.Methods: Male Sprague-Dawley rats were randomly divided into sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. Each exercise group had 3 subgroups that were sacrificed for cardiac tissue analyses at 1, 4, and 8 weeks, respectively, and all rats participated in a daily 1 h treadmill routine 5 days per week. Echocardiographic measurements were performed 24 h after the last exercise session. Additionally, myocardium samples and blood were collected for histological and biochemical examinations. Changes in the extracellular signal-regulated kinases 1/2 (ERK1/2) signal pathway were detected by Western blotting.Results: After a week of running, ventricular myocyte size and the phosphorylation of ERK1/2 increased in the HIR group, while left ventricular (LV) diastolic diameter values and LV relative wall thickness increased in the LIR and MIR groups. In addition, we observed heart enlargement, cTnI decrease, and ERK1/2 signal activation in each of the exercise groups after 4 weeks of running. However, the HIR group displayed substantial rupture and increased fibrosis in myocardial tissue. In addition, compared with the LIR and MIR groups, 8 weeks of HIR resulted in structural damage, fiber deposition, and increased cTnI. However, there was no difference in the activation of ERK1/2 signaling between the exercise and SED groups.Conclusion: The effect of running on cardiac hypertrophy was intensity dependent. In contrast to LIR and MIR, the cardiac hypertrophy induced by 8 weeks of HIR was characterized by potential cardiomyocyte injury, which increased the risk of pathological development. Furthermore, the ERK signaling pathway was mainly involved in the compensatory hypertrophy process of the myocardium in the early stage of exercise and was positively correlated with exercise load. However, long-term exercise may attenuate ERK signaling activation.

The predominant pathological manifestation of osteoarthritis (OA) is articular cartilage damage. Chondrocytes are the only cell type present in articular cartilage. The proportion of chondrocytes inflammation and apoptosis correlated significantly with the degree of articular cartilage degeneration and progression of OA. Irisin is released from myocytes during physical activity, and acts as a link between muscles and other tissues and organs. Many studies have confirmed the multifunctional role of Irisin and the beneficial effects of this molecule on bone development and regeneration. Little is known about the mechanisms of Irisin on chondrocytes and the development of OA. This study aimed to investigate the mechanisms and effects of Irisin on interleukin-1β (IL-1β)-induced rat chondrocytes. Our results revealed that Irisin improved IL-1β-induced growth inhibition in chondrocytes and attenuated the production of reactive oxygen species (ROS). And Irisin decreased the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and exerted anti-apoptotic effects by the extracellular signal-regulated kinases (ERK) signaling pathway. In conclusion, Irisin acts through the ERK signaling pathway to protect against IL-1β-induced chondrocytes injury by reducing excessive ROS, inhibiting inflammation and apoptosis. The present study sheds new light on the chondroprotective actions of this myokine, and further develops the therapeutic targets of Irisin for bone and cartilage disorders including OA.

Purpose: Exercise is an effective intervention for both the prevention and treatment of cardiovascular diseases. In this study, we investigated the structural and functional changes that occur in cardiac response and how they differ with various exercise intensities, hence exploring the potential signal transduction.Methods: Male Sprague–Dawley rats were randomly divided into the sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. Each exercise group had 3 different operation time subgroups for 1, 4, and 8 weeks, respectively, and all rats observed a daily 1 h treadmill routine 5 days per week. Echocardiographic measurements were performed at the end of the experimental program. Additionally, myocardium samples and blood were collected for histological and biochemical examinations. Changes in the extracellular signal-regulated kinases 1/2 (ERK1/2) signal pathway were detected by Western blotting.Results: After a week of running, ventricular myocyte size and the phosphorylation of ERK1/2 increased in the HIR group, while left ventricular (LV) diastolic diameter values and LV relative wall thickness increased in the LIR and MIR groups. In addition, we observed heart enlargement, cTnI decrease, and ERK1/2 signal activation in each of the exercise groups after 4 weeks of running. However, the HIR group displayed a substantial rupture and increased fibrosis in myocardial tissue. In addition, compared with the LIR and MIR groups, 8 weeks of HIR resulted in structural damage, fiber deposition, and increased cTnI. However, there was no difference in activation of ERK1/2 signaling between the exercise groups and SED group.Conclusions: The effect of running on cardiac hypertrophy was intensity dependent. In contrast to LIR and MIR, 8 weeks of HIR-induced cardiac hypertrophy was characterized by potential cardiomyocyte injury, which increased the risk of pathological development. Furthermore, the ERK signaling pathway was mainly involved in the compensatory hypertrophy process of the myocardium in the early stage of exercise and was positively correlated with exercise load. However, long-term exercise may attenuate ERK signaling activation.