Targeted Therapy of Osteoarthritis via Intra‐Articular Delivery of Lipid‐Nanoparticle‐Encapsulated Recombinant Human FGF18 mRNA
Fibroblast growth factor 18 (FGF18) emerges as a promising therapeutic target for osteoarthritis (OA). In this study, a novel articular cavity-localized lipid nanoparticle (LNP) named WG-PL14 is developed. This optimized formulation has a nearly 30-fold increase in mRNA expression as well as better articular cavity enrichment compared to commercial lipids MC3 when performing intra-articular injection. Then, a mRNA sequence encoding recombinant human FGF18 (rhFGF18) for potential mRNA therapy in OA is optimized. In vitro assays confirm the translation of rhFGF18 mRNA into functional proteins within rat and human chondrocytes, promoting cell proliferation and extracellular matrix (ECM) synthesis. Subsequently, the therapeutic efficacy of the LNP-rhFGF18 mRNA complex is systematically assessed in a mouse OA model. The administration exhibits several positive outcomes, including an improved pain response, upregulation of ECM-related genes (e.g., AGRN and HAS2), and remodeling of subchondral bone homeostasis compared to a control group. Taken together, these findings underscore the potential of localized LNP-rhFGF18 mRNA therapy in promoting the regeneration of cartilage tissue and mitigating the progression of OA.
Authors
- M J Sun (ORCID: https://orcid.org/0009-0006-9155-726X)
- Xiaoqing Hu (ORCID: https://orcid.org/0000-0001-9824-1109)
- Zihang Pan (ORCID: https://orcid.org/0000-0003-4195-7207)
- Xiaoxia Li (ORCID: https://orcid.org/0000-0002-4872-9525)
- Lei Miao (ORCID: https://orcid.org/0000-0002-2281-2689)
- Liangliang Tian (ORCID: https://orcid.org/0000-0003-0893-6420)
- Kai Wang (ORCID: https://orcid.org/0000-0001-6240-0147)
- Xi Wang (ORCID: https://orcid.org/0000-0003-3415-7092)
- Bin Ma (ORCID: https://orcid.org/0000-0002-3913-0545)
- Junyan Wang (ORCID: https://orcid.org/0009-0007-1047-3783)
- Xiaohong Peng (ORCID: https://orcid.org/0000-0002-8902-6463)
- Weijing Kong (ORCID: https://orcid.org/0000-0002-4854-6219)
- Cheng Jin (ORCID: https://orcid.org/0009-0008-2847-7157)
- Boyang Xu
- Yun Zhao (ORCID: https://orcid.org/0000-0002-7550-2158)
- Yifei Fan (ORCID: https://orcid.org/0000-0001-7367-7045)
- Yingfang Ao (ORCID: https://orcid.org/0000-0001-8103-5050)
- Quanyi Guo
Institutions
- Peking University (CN)
- Chinese PLA General Hospital (CN)
- Peking University Third Hospital (CN)
Publication Details
- Journal
- Advanced Healthcare Materials
- Published
- 2024-10-04
- DOI
- https://doi.org/10.1002/adhm.202400804
- Citations
- 19
- Primary Topic
- Fibroblast Growth Factor Research
- Type
- article
- Field-Weighted Citation Impact
- 4.44
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Beijing Municipality
- Beijing Municipal Science and Technology Commission
- Beijing Nova Program
- Key Technologies Research and Development Program
- Fundamental Research Funds for the Central Universities