The role of the NOTCH1 signaling pathway in the maintenance of mesenchymal stem cell stemness and chondrocyte differentiation and its potential in the treatment of osteoarthritis.
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Abstract
Objective: This study aims to explore the potential role of mesenchymal stem cells (MSCs) in the treatment of osteoarthritis (OA), particularly the function of the NOTCH1 signaling pathway in maintaining the stemness of MSCs and in chondrocyte differentiation.
Methods: Utilizing diverse analytical techniques on an osteoarthritis dataset, we unveil distinct gene expression patterns and regulatory relationships, shedding light on potential mechanisms underlying the disease. Techniques used include the culture of MSCs, induction of differentiation into chondrocytes, establishment of stable cell lines, Western Blot, and immunofluorescence. Through the construction of lentiviruses overexpressing and knocking out NOTCH1, the effects of NOTCH1 on the stemness of MSCs and chondrocyte differentiation were investigated. Additionally, the effects of NOTCH1 on chondrocyte homeostasis and apoptosis were evaluated by adding the EZH2 inhibitor GSK126 and the endoplasmic reticulum stress inducer tunicamycin.
Results: Experimental results demonstrated that NOTCH1 expression can influence the maintenance of MSC stemness and chondrocyte differentiation by regulating EZH2. Knockout of NOTCH1 decreased the expression of chondrocyte markers, while overexpression increased their expression. Under conditions of endoplasmic reticulum stress, NOTCH1 expression helped reduce the expression of stress-related proteins, maintain chondrocyte homeostasis, and inhibit apoptosis.
Conclusion: The NOTCH1 signaling pathway plays a crucial role in maintaining the stemness of MSCs, differentiating into chondrocytes, and in the treatment of osteoarthritis. NOTCH1 influences the differentiation fate of MSCs and the homeostasis of chondrocytes by regulating EZH2 and other related genes, offering new targets and strategies for the treatment of diseases like osteoarthritis.
期刊介绍：
Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues.
Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications.
JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.
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