RESUMO
A balance between muscle injury and regeneration is critical for sustaining muscle function during myogenesis. Melatonin is well recognized for its involvement in neuroprotective activities, immune system regulation and suppression of inflammatory responses. This study set out to provide evidence that melatonin improves muscle regeneration during skeletal muscle differentiation. We began with cloning a stable cell line expressing Pax7 knockdown C2C12 cells. We then investigated markers of muscle degradation and regeneration after treating growth medium and differentiated medium with melatonin. Bioinformatics analysis of RNA sequencing results revealed that melatonin regulates muscle differentiation and that Wnt cascades are involved in the mechanism of muscle differentiation. Screening of miRNA online databases revealed that miR-3475-3p is a specific binding site on Pax7 and acts as a negative regulator of Pax7, which is involved in melatonin-induced muscle differentiation. We then investigated the effects of melatonin treatment in the early stage of glycerol-induced skeletal muscle injury in mice. Rotarod performance, micro-computed tomography and immunohistochemistry findings showed that melatonin-induced increases in Pax7 expression rapidly rescue skeletal muscle differentiation and improve muscle fiber morphology in glycerol-induced muscle injury. Our data support the hypothesis that melatonin rapidly rescues skeletal muscle differentiation and the melatonin/Pax7 axis could therefore serve as an important therapeutic target to optimize muscle healing after injury.
Assuntos
Melatonina , Animais , Camundongos , Melatonina/farmacologia , Melatonina/uso terapêutico , Melatonina/metabolismo , Glicerol/metabolismo , Microtomografia por Raio-X , Mioblastos/metabolismo , Diferenciação Celular/genética , Músculo Esquelético , Desenvolvimento Muscular/genética , Proliferação de Células , Fator de Transcrição PAX7/genética , Fator de Transcrição PAX7/metabolismoRESUMO
Rheumatoid arthritis (RA) is a common autoimmune disease marked by immune cell activation and chronic inflammation in the synovium accompanied by osteoclast activation and local joint destruction. Increased levels of the adipokine nesfatin-1 in RA synovium are associated with proinflammatory cytokines. Our analysis of datasets from the Gene Expression Omnibus (GEO) database and synovial tissue samples from RA patients revealed that these had higher levels of nesfatin-1 and osteoclast markers compared with normal synovium. These findings were the same in tissue samples from mice with collagen-induced arthritis (CIA) and normal healthy controls. RNA sequencing analysis revealed that nesfatin-1 increased levels of bone morphogenetic protein-5 (BMP5) expression via JAK/STAT signaling in RA synovial fibroblasts. Finally, we found that nesfatin-1 short hairpin RNA reduced BMP5 and osteoclast formation in CIA mice. These findings provide new insights into the pathogenesis of RA.
Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Camundongos , Artrite Experimental/genética , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Fibroblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese , Membrana Sinovial/metabolismoRESUMO
Rheumatoid arthritis (RA) is a prototypic inflammatory disease, characterized by the infiltration of proinflammatory cytokines into the joint synovium and the migration of mononuclear cells into inflammatory sites. The adipokine nesfatin-1 is linked to inflammatory events in various diseases, although its role in RA pathology is uncertain. Analysis of the Gene Expression Omnibus GSE55235 dataset revealed high levels of expression of the adipokine nesfatin-1 in human RA synovial tissue. Similarly, our human synovial tissue samples exhibited increasing levels of nesfatin-1 expression and Ccl2 mRNA expression. Nesfatin-1-induced stimulation of CCL2 expression and monocyte migration involved the MEK/ERK, p38, and NF-κB signaling pathways. Notably, nesfatin-1-induced increases in CCL2 expression favored M1 macrophage polarization, which increased the expression of proinflammatory cytokines IL-1ß, IL-6, and TNF-α. Finally, nesfatin-1 shRNA ameliorated the severity of inflammatory disease and reduced levels of M1 macrophage expression in CIA mice. Our studies confirm that nesfatin-1 appears to be worth targeting in RA treatment.
Assuntos
Artrite Reumatoide , Monócitos , Humanos , Camundongos , Animais , Monócitos/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo , Adipocinas/metabolismo , Quimiocina CCL2/metabolismoRESUMO
Cataracts, a prevalent age-related eye condition, pose a significant global health concern, with rising rates due to an aging population and increased digital device usage. In Taiwan, cataract prevalence is particularly high, reaching up to 90% among individuals aged 70 and above. The lens of the eye absorbs short-wave light, which can lead to oxidative stress in lens epithelial cells and contribute to cataract formation. Exposure to ultraviolet (UV) light further exacerbates the risk of cataracts by generating reactive oxygen species. Heat-shock proteins (HSPs), involved in protein maintenance and repair, have been linked to cataract development. Cordyceps cicadae (C. cicadae), a traditional Chinese medicine, has a long history of use and is known for its pharmacological effects. N6-(2-hydroxyethyl) adenosine (HEA), a bioactive compound found in C. cicadae, exhibits anti-inflammatory, immunomodulatory, and neuroprotective properties. Previous studies have shown that C. cicadae mycelial extracts improve dry eye disease and reduce intraocular pressure in animal models. Additionally, C. cicadae possesses antioxidant properties, which are beneficial for combating cataract formation. In this study, we aim to evaluate the preventive efficacy of C. cicadae mycelial extracts in UV-induced cataract development. By investigating the ameliorative effects of C. cicadae on eye diseases and its potential role in ocular health improvement, we hope to uncover new options for cataract prevention and provide insights into the mechanisms of action. The findings of this research could provide a novel approach for nutritional supplements targeting cataract prevention, offering potential benefits in the field of ocular health.
Assuntos
Catarata , Cordyceps , Camundongos , Animais , Antioxidantes/farmacologia , Estresse Oxidativo , Adenosina , Catarata/etiologia , Catarata/prevenção & controleRESUMO
Osteoarthritis (OA) is a prevalent joint disease commonly associated with aging and obesity, which can lead to pain, stiffness, joint dysfunction, and disability. Omentin-1 (also called intelectin-1) is a newly discovered adipokine, which plays a protective role in suppressing the secretion of pro-inflammatory cytokines. Based on data from the Gene Expression Omnibus (GEO) dataset and clinical samples obtained at our institution revealed, determined that omentin-1 and IL-4 (an anti-inflammatory cytokine) levels were significantly lower in OA patients than in normal controls. Omentin-1 was shown to induce IL-4-depedent anti-inflammatory responses and M2 macrophage polarization in OA synovial fibroblasts via the PI3K, ERK, and AMPK pathways. Administering omentin-1 was shown to block cartilage degradation and bone erosion resulting from anterior cruciate ligament transection by inhibiting the production of pro-inflammatory cytokines and promoting M2 macrophage polarization in vivo. Our findings indicate omentin-1 as a promising therapeutic avenue for the treatment for OA.
Assuntos
Citocinas , Interleucina-4 , Macrófagos , Osteoartrite , Humanos , Citocinas/metabolismo , Interleucina-4/imunologia , Macrófagos/imunologia , Osteoartrite/imunologiaRESUMO
Recent literature highlights the importance of microRNAs (miRNAs) functioning as diagnostic biomarkers and therapeutic agents in osteoarthritis (OA) and regulators of gene expression. In OA pathogenesis, cell adhesion molecules (CAMs), especially vascular cell adhesion protein 1 (VCAM-1), recruit monocyte infiltration to inflamed synovial tissues and thus accelerate OA progression. Up until now, little has been known about the regulatory mechanisms between miRNAs, long non-coding RNAs (lncRNAs) and VCAM-1 during OA progression. The evidence in this article emphasizes that the functional feature of miR-150-5p is an interaction with the lncRNA X-inactive specific transcript (XIST), which regulates VCAM-1-dependent monocyte adherence in OA synovial fibroblasts (OASFs). Levels of VCAM-1, CD11b (a monocyte marker) and XIST expression were higher in human synovial tissue samples and OASFs, while levels of miR-150-5p were lower in human OA synovial tissue compared with non-OA specimens. XIST enhanced VCAM-1-dependent monocyte adherence to OASFs. Upregulation of miR-150-5p inhibited the effects of XIST upon monocyte adherence. Administration of miR-150-5p effectively ameliorated OA severity in anterior cruciate ligament transection (ACLT) rats. The interaction of miR-150-5p and XIST regulated VCAM-1-dependent monocyte adherence and attenuated OA progression. Our findings suggest that miR-150-5p is a promising small-molecule therapeutic strategy for OA.
Assuntos
MicroRNAs , Osteoartrite , RNA Longo não Codificante/metabolismo , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Monócitos/metabolismo , Osteoartrite/metabolismo , Osteoartrite/terapia , RNA Longo não Codificante/genética , Ratos , Molécula 1 de Adesão de Célula VascularRESUMO
Osteoarthritis (OA) is a painful, progressive chronic inflammatory disease marked by cartilage destruction. Certain synovial inflammatory cytokines, such as IL-1ß and TNF-α, promote OA inflammation and pain. Lactobacillus spp. is a well-known probiotic with anti-inflammatory, analgesic, antioxidant, and antiosteoporotic properties. This study evaluated the therapeutic effects of a live L. plantarum strain (GKD7) in the anterior cruciate ligament transection (ACLT)-induced OA rat model. The results show that oral administration of live L. plantarum GKD7 improved weight-bearing asymmetry after ACLT surgery. Moreover, micro-computed tomography images and histopathological analysis show that oral live L. plantarum GKD7 improved subchondral bone architecture, protected articular cartilage against ACLT-induced damage, and reduced synovial inflammation. L. plantarum GKD7 also reduced IL-1ß and TNF-α production in OA cartilage and synovium. Thus, orally administered live L. plantarum GKD7 appears to effectively slow the progression of OA.
Assuntos
Cartilagem Articular , Lactobacillus plantarum , Osteoartrite do Joelho , Animais , Modelos Animais de Doenças , Inflamação/patologia , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/terapia , Ratos , Fator de Necrose Tumoral alfa/farmacologia , Microtomografia por Raio-XRESUMO
Osteoarthritis (OA) is represented by the accumulation and adhesion of M1 macrophages into synovium tissues in the joint microenvironment and subsequent inflammatory response. Cordycerebroside A, a cerebroside compound isolated from Cordyceps militaris, exhibits anti-inflammatory activity, but has not yet been examined in M1 macrophages during OA disease. Our results indicate higher expression of M1 macrophage markers in synovium tissue from OA patients compared with normal healthy controls. Records from the Gene Expression Omnibus (GEO) data set and our clinic samples revealed higher levels of ICAM-1 (a critical adhesion molecule during OA disease) and CD86 (a M1 macrophage marker) in OA synovial tissue than in healthy tissue. The same effects were found in rats with OA induced by anterior cruciate ligament transaction (ACLT). We also found that cordycerebroside A inhibited ICAM-1 synthesis and antagonized M1 macrophage adhesion to OA synovial fibroblasts by inhibiting the ERK/AP-1 pathway. Thus, cordycerebroside A displayed novel anti-arthritic effects. PRACTICAL APPLICATIONS: Here we report a higher level of M1 macrophage markers and ICAM-1 in synovium tissue from OA patients compared with normal healthy controls by using GEO data set and our clinic samples. The same effects were revealed in rats with OA induced by ACLT. Cordycerebroside A significantly suppressed ICAM-1 production and diminished M1 macrophage adhesion to OA synovial fibroblasts. Therefore, cordycerebroside A exhibited novel anti-OA functions.