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Multifunctional hydrogels: advanced therapeutic tools for osteochondral regeneration
Wenqian Zhang,Kangkang Zha,Weixian Hu,Yuan Xiong,Samuel Knoedler,Doha Obed,Adriana C. Panayi,Ze Lin,Faqi Cao,Bobin Mi,Guohui Liu 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Various joint pathologies such as osteochondritis dissecans, osteonecrosis, rheumatic disease, and trauma, may result in severe damage of articular cartilage and other joint structures, ranging from focal defects to osteoarthritis (OA). The osteochondral unit is one of the critical actors in this pathophysiological process. New approaches and applications in tissue engineering and regenerative medicine continue to drive the development of OA treatment. Hydrogel scaffolds, a component of tissue engineering, play an indispensable role in osteochondral regeneration. In this review, tissue engineering strategies regarding osteochondral regeneration were highlighted and summarized. The application of hydrogels for osteochondral regeneration within the last five years was evaluated with an emphasis on functionalized physical and chemical properties of hydrogel scaffolds, functionalized delivery hydrogel scaffolds as well as functionalized intelligent response hydrogel scaffolds. Lastly, to serve as guidance for future efforts in the creation of bioinspired hydrogel scaffolds, a succinct summary and new views for specific mechanisms, applications, and existing limitations of the newly designed functionalized hydrogel scaffolds were offered.
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Hu Liangcong,Xie Xudong,Xue Hang,Wang Tiantian,Panayi Adriana C.,Lin Ze,Xiong Yuan,Cao Faqi,Yan Chengcheng,Chen Lang,Cheng Peng,Zha Kangkang,Sun Yun,Liu Guodong,Yu Chenyan,Hu Yiqiang,Tao Ranyang,Zhou 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
MicroRNAs (miRNAs) broadly regulate normal biological functions of bone and the progression of fracture healing and osteoporosis. Recently, it has been reported that miR-1224-5p in fracture plasma is a potential therapy for osteogenesis. To investigate the roles of miR-1224-5p and the Rap1 signaling pathway in fracture healing and osteoporosis development and progression, we used BMMs, BMSCs, and skull osteoblast precursor cells for in vitro osteogenesis and osteoclastogenesis studies. Osteoblastogenesis and osteoclastogenesis were detected by ALP, ARS, and TRAP staining and bone slice resorption pit assays. The miR-1224-5p target gene was assessed by siRNA-mediated target gene knockdown and luciferase reporter assays. To explore the Rap1 pathway, we performed high-throughput sequencing, western blotting, RT-PCR, chromatin immunoprecipitation assays and immunohistochemical staining. In vivo, bone healing was judged by the cortical femoral defect, cranial bone defect and femoral fracture models. Progression of osteoporosis was evaluated by an ovariectomy model and an aged osteoporosis model. We discovered that the expression of miR-1224-5p was positively correlated with fracture healing progression. Moreover, in vitro, overexpression of miR-1224-5p slowed Rankl-induced osteoclast differentiation and promoted osteoblast differentiation via the Rap1-signaling pathway by targeting ADCY2. In addition, in vivo overexpression of miR-1224-5p significantly promoted fracture healing and ameliorated the progression of osteoporosis caused by estrogen deficiency or aging. Furthermore, knockdown of miRNA-1224-5p inhibited bone regeneration in mice and accelerated the progression of osteoporosis in elderly mice. Taken together, these results identify miR-1224-5p as a key bone osteogenic regulator, which may be a potential therapeutic target for osteoporosis and fracture nonunion.
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