Crab shell polypeptides enhance calcium dynamics and osteogenic activity in osteoporosis

Xiaolei Dong¹Guangmin Zhang¹Chong Sun²Hui Zhang³Jinmeng Zhen³Xinlei Li⁴Xiaohui Xu¹Jiane Liu⁵Xiangzhong Zhao⁶Ming Yi Zhang¹Linlin Liu¹Shaoqi Tian⁷Daijie Wang⁸Zheng Wang^1*Bing Li^1*

• ¹Department of Genetics and Cell Biology, School of Basic Medicine, Qingdao University, Qingdao, China
• ²Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
• ³Department of Medicinal Chemistry, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
• ⁴Department of Pharmaceutical Analysis, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
• ⁵Department of Reproductive Medicine, the Affiliated Hospital of Qingdao University, Qingdao, China
• ⁶Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, China
• ⁷Department of Orthopedic Operation, the Affiliated Hospital of Qingdao University, Qingdao, China
• ⁸International Joint Laboratory of Medicinal Food R&D and Health Products Creation/Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology, Heze, China

Osteoporosis (OP) is a chronic, systemic skeletal disorder characterized by progressive bone loss and microarchitectural deterioration, which increases fracture susceptibility and presents a challenging set of global healthcare problems. Current pharmacological interventions are limited by adverse effects, high costs, and insufficient long-term efficacy. Here, we identify snow crab shell-derived polypeptides (SCSP) as a potent osteoprotective agent. SCSP, enriched in glutamic acid, aspartic acid, and lysine, significantly enhances bone mineral density, restores trabecular architecture, and preserves bone tissue integrity in an ovariectomy-induced OP mouse model without detectable systemic toxicity. At the molecular level, SCSP treatment induces the expression cell cycle regulators and motor protein pathways in osteoblasts while suppressing proinflammatory signaling networks, thereby re-establishing osteoblast-osteoclast balance and restoring calcium and phosphorus homeostasis. This combined mechanism promotes osteogenesis while simultaneously suppressing adipogenesis. Our findings position SCSP as a promising natural therapeutic for OP and provide key mechanistic insights that may guide future bone-targeted interventions.