Greening Bone Healing: The Emerging Role of Plant-Derived Exosome-Like Nanoparticles in Osteoporosis and Osteoarthritis Therapy

Shuai Yuan,1,* Da-Wei He,1,* Xiao-Jie Zhou,1 Hao-Tian Jiao,1,2 Yan Gao,1 Chong Li1 1Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Orthopedics, the First People’s Hospital of Kunshan, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Gao, Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, No. 566 East of Qianjin Road, Suzhou, Jiangsu, 215300, People’s Republic of China, Tel +86 0512 5753 2362, Email ygao1106@alu.suda.edu.cn Chong Li, Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, No. 566 East of Qianjin Road, Suzhou, Jiangsu, 215300, People’s Republic of China, Tel +86 0512 5753 2362, Email lichong1705@163.comAbstract: Plant-derived exosome-like nanoparticles (PDENs) have demonstrated unique advantages in the prevention and treatment of osteoporosis and osteoarthritis in recent years. This review systematically summarizes the biological properties of PDENs, methods for their isolation and purification, molecular composition, and their mechanisms of action in bone and joint tissue repair. Current evidence indicates that PDENs can maintain bone homeostasis by promoting the proliferation and differentiation of osteoblasts, inhibiting osteoclast activity, modulating osteogenic differentiation of mesenchymal stem cells, and stimulating angiogenesis. In the context of osteoarthritis, PDENs enhance joint repair by facilitating chondrocyte regeneration, modulating inflammatory responses, and improving extracellular matrix metabolism. Despite the promising therapeutic potential of PDENs in the treatment of bone- and joint-related diseases, challenges remain regarding their precise mechanisms of action, standardization of preparation, and clinical translation. Future research should focus on elucidating the underlying mechanisms, establishing robust quality control methodologies, and conducting comprehensive preclinical evaluations to pave the way for their clinical application.Keywords: plant-derived exosomes, nanocarriers, osteoporosis, osteoarthritis, tissue repair