Simultaneously Modulating HIF-1α and HIF-2α and Optimizing Macrophage Polarization through the Biomimetic Gene Vector toward the Treatment of Osteoarthritis
Source abstract
Abstract
In osteoarthritis (OA), articular cartilage is continuously submerged in a hypoxic environment throughout life, and hypoxia-inducible factors (HIFs) play a crucial role in OA progression. Among the various HIF phenotypes, HIF-1α positively contributes to maintaining the stability of the articular cartilage matrix. In contrast, HIF-2α has a detrimental effect, leading to chondrocyte apoptosis and exacerbating inflammation. Notably, there is currently no simultaneous regulation of HIF-1α and HIF-2α for OA treatment. Thus, the biomimetic gene vector (MENP) was developed for co-delivery of siHIF-2α and Mg 2+ to the inflamed regions in OA joints, comprising an inner core consisting of siHIF-2α and Mg 2+ and an outer M2 macrophage membrane. In vitro and in vivo studies demonstrate that MENP effectively targets inflamed areas, efficiently silences HIF-2α, and facilitates HIF-1α-mediated cartilage restoration through Mg 2+ . Furthermore, it indirectly promotes the polarization of macrophages toward an anti-inflammatory M2 phenotype through its action on inflamed synoviocytes. Overall, MENP is an efficient biomimetic vehicle for alleviating inflammation and promoting cartilage repair, representing an appealing approach for OA treatment.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Osteoarthritis Treatment and Mechanisms · Bone and Joint Diseases · Bone Metabolism and Diseases
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Jinan University, 510630 Guangzhou, China.
Department of Psychology, Li Ka Shing Faculty of Medicine, State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China.
Joint Laboratory of Chinese Herbal Glycoengineering and Testing Technology, University of Macau and National Glycoengineering Research Center, Macao, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao, China.
Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 200072 Shanghai, China.
Funding
National Key Research and Development Program of China · National Natural Science Foundation of China · Natural Science Foundation of Guangdong Province · Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University · Science and Technology Projects in Guangzhou · the Fundamental Research Funds for the Central Universities · uangdong Medical Science and Technology Research Fund Project · Special Funds for the Basic Research and Development Program in the Central Non-profit Research Institutesof China
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