Acetyl-11-keto-ß-boswellic acid restrains the progression of synovitis in osteoarthritis via the Nrf2/HO-1 pathway.

Synovial inflammation plays a key role in osteoarthritis (OA) pathogenesis. Fibroblast-like synoviocytes (FLSs) represent a distinct cell subpopulation within the synovium, and their unique phenotypic alterations are considered significant contributors to inflammation and fibrotic responses. The underlying mechanism by which acetyl-11-keto-ß-boswellic acid (AKBA) modulates FLS activation remains unclear. This study aims to assess the beneficial effects of AKBA through both in vitro and in vivo investigations. Network pharmacology evaluation is used to identify potential targets of AKBA in OA. We evaluate the effects of AKBA on FLSs activation in vitro and the regulatory role of AKBA on the Nrf2/HO-1 signaling pathway. ML385 (an Nrf2 inhibitor) is used to verify the binding of AKBA to its target in FLSs. We validate the in vivo efficacy of AKBA in alleviating OA using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT+DMM) in a rat model. Network pharmacological analysis reveals the potential effect of AKBA on OA. AKBA effectively attenuates lipopolysaccharide (LPS)-induced abnormal migration and invasion and the production of inflammatory mediators, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) in FLSs, contributing to the restoration of the synovial microenvironment. After treatment with ML385, the effect of AKBA on FLSs is reversed. In vivo studies demonstrate that AKBA mitigates synovial inflammation and fibrotic responses induced by ACLT+DMM in rats via activation of the Nrf2/HO-1 axis. AKBA exhibits theoretical potential for alleviating OA progression through the Nrf2/HO-1 pathway and represents a viable therapeutic candidate for this patient population.

Role of oxidative stress in the concurrent development of osteoporosis and tendinopathy: Emerging challenges and prospects for treatment modalities.

Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.

Antioxidant and anti-inflammatory injectable hydrogel microspheres for in situ treatment of tendinopathy.

Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life. Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of tendinopathy. Herein, injectable methacrylate gelatin (GelMA) microspheres (GM) were fabricated and loaded with heparin-dopamine conjugate (HDC) and hepatocyte growth factor (HGF). GM@HDC@HGF were designed to balance the inflammatory microenvironment by inhibiting oxidative stress and inflammation, thereby regulating extracellular matrix (ECM) metabolism and halting tendon degeneration. Combining growth factors with heparin was expected to improve the encapsulation rate and maintain the long-term efficacy of HGF. In addition, the catechol groups on dopamine have adhesion and antioxidant properties, allowing potential attachment at the injured site, and better function synergized with HGF. GM@HDC@HGF injected in situ in rat Achilles tendinopathy (AT) models significantly down-regulated oxidative stress and inflammation, and ameliorated ECM degradation. In conclusion, the multifunctional platform developed presents a promising alternative for the treatment of tendinopathy.

Erxian Decoction-induced serum exosomes slowed bone marrow mesenchymal stem cell senescence through mitophagy.

OBJECTIVE: Erxian Decoction (EXD) is traditionally employed in the treatment of menopausal syndromes, although its underlying mechanisms remain largely undefined. Given that the senescence of bone marrow mesenchymal stem cells (BMSCs) is intertwined with organismal aging and associated diseases, this study endeavored to elucidate the influence of EXD on aging BMSCs and uncover the mechanisms through which EXD impedes BMSC senescence. METHODS: Initially, we probed the anti-senescent mechanisms of EXD on BMSCs via network pharmacology. We subsequently isolated and identified exosomes from the serum of EXD-fed rats (EXD-Exos) and administered these to H2 O2 -induced aging BMSC. Assays were conducted to assess BMSC senescence indicators and markers pertinent to mitochondrial autophagy. Treatments with mitophagy inhibitors and activators were then employed to substantiate our findings. RESULTS: Protein-protein interaction (PPI) network analyses spotlighted AKT1, TP53, TNF, JUN, VEGFA, IL6, CASP3 and EGFR as focal targets. Gene Ontology and Kyoto Encylcopedia of Genes and Genomes pathway analyses underscored oxidative stress, mitophagy and cell proliferation as pivotal processes. Our cellular assays ascertained that EXD-Exos mitigated H2 O2 -induced senescence phenotypes in BMSCs. Moreover, EXD-Exos ameliorated disrupted mitophagy in BMSCs, as evidenced by enhanced cellular membrane potential and diminished reactive oxygen species levels. Intriguingly, EXD-Exos also preserved the osteogenic differentiation potential of BMSCs while curtailing their adipogenic propensity. CONCLUSION: Our findings compellingly suggest that EXD counteracts BMSC senescence by fostering mitophagy.

Progress in studying the impact of hyperlipidemia and statins on rotator cuff injury and repair.

This review delves into the intersection of two prevalent conditions, hyperlipidemia and rotator cuff injuries, both of which bear substantial healthcare burdens. Our investigation begins with an exploration of rotator cuff injuries, common musculoskeletal disorders that severely impair shoulder functionality and quality of life. These injuries are notably pervasive among sports enthusiasts and the older adult, with an incidence rate estimated at 5-10% in the general population. Despite their widespread occurrence and the diverse, multifactorial etiological factors, effective treatment strategies remain elusive. We then examine hyperlipidemia, a metabolic disorder affecting approximately 40% of the global adult population. Characterized by elevated levels of cholesterol and triglycerides, hyperlipidemia can precipitate severe cardiovascular complications and presents a significant socioeconomic burden. Although current management strategies encompass lifestyle modifications and pharmacological interventions, the condition remains a formidable health challenge. Central to this review is the exploration of a potential association between hyperlipidemia and rotator cuff injuries. We aim to synthesize the current understanding of hyperlipidemia's role in the pathophysiology of rotator cuff injuries, thereby offering fresh insights into their common etiological underpinnings, potential therapeutic targets, and drugs, such as Statins. The influence of other lipid-lowering therapeutics on tendon health is also considered, and further research into the molecular pathways and potential therapeutic benefits of these drugs is required. This pursuit aligns with broader efforts to enhance patient outcomes, minimize healthcare burdens, and contribute to the global understanding of these prevalent conditions.

Translational studies of exosomes in sports medicine - a mini-review.

This review in sports medicine focuses on the critical role of exosomes in managing chronic conditions and enhancing athletic performance. Exosomes, small vesicles produced by various cells, are essential for cellular communication and transporting molecules like proteins and nucleic acids. Originating from the endoplasmic reticulum, they play a vital role in modulating inflammation and tissue repair. Their significance in sports medicine is increasingly recognized, particularly in healing athletic injuries, improving articular cartilage lesions, and osteoarthritic conditions by modulating cellular behavior and aiding tissue regeneration. Investigations also highlight their potential in boosting athletic performance, especially through myocytes-derived exosomes that may enhance adaptability to physical training. Emphasizing a multidisciplinary approach, this review underlines the need to thoroughly understand exosome biology, including their pathways and classifications, to fully exploit their therapeutic potential. It outlines future directions in sports medicine, focusing on personalized treatments, clinical evaluations, and embracing technological advancements. This research represents a frontier in using exosomes to improve athletes' health and performance capabilities.

Nanofat functionalized injectable super-lubricating microfluidic microspheres for treatment of osteoarthritis.

Nanofat (NF) is a fine emulsion that has been used to treat a variety of diseases given its abundance of bioactive components. However, the biological functions of NF have been limited due to its inability to localize during implantation. In this study, NF was immobilized in microfluidic-generated aldehyde-modified polylactic glycolic acid (PLGA) porous microspheres (PMs) via Schiff base condensation and non-covalent binding in a three-dimensional (3D) porous network (PMs@NF). The PMs effectively enhanced the cartilage-targeted retention efficiency of NF, which also resulted in remarkable lubrication performance, with the friction coefficient being reduced by ∼80%, which was maintained over time. Meanwhile, the 3D penetrating structure of the microspheres stimulated cytokine secretion by the NF-derived stem cells, upregulating the expression of anabolism-related genes and downregulating catabolism, and the expression of inflammation-related and pain-related genes. Injecting PMs@NF into the knee joint cavity of a rat model with destabilization of the medial meniscus (DMM) reduced osteophyte formation and protected the cartilage from degeneration, thereby inhibiting the progression of osteoarthritis and improving animal behavior. In summary, this study developed a multifunctional platform with NF immobilization and super-lubrication, which showed great potential for the minimally invasive treatment of osteoarthritis.