Aqueous extract of Sedum sarmentosum (SS-Ex) promotes bone formation and linear bone growth in a calcium/vitamin D-deficient mouse model

Proper bone development during the growth phase is essential for achieving normal skeletal length, mineral density, and strength, which is regulated by growth hormones, vitamin D, and calcium. Deficiencies in these elements can impair skeletal formation, increasing the risk of disorders such as rickets and osteoporosis. Therefore, natural compounds with bone-supportive effects are of growing interest. Sedum sarmentosum (S. sarmentosum), a plant traditionally used in Korea to treat liver disorders, contains abundant vitamin C and calcium, however, its effects on bone development remain unclear. We found that oral administration of an aqueous extract of S. sarmentosum (SS-Ex) improved trabecular bone structure and bone mineral density in mice fed a calcium- and vitamin D-deficient diet. SS-Ex treated mice showed increased growth plate thickness and elevated serum levels of osteocalcin (Ocn), type I collagen alpha 1 (Col1a1), calcium, and calcitonin. In vitro, SS-Ex enhanced alkaline phosphatase (Alp) activity and promoted mineral deposition in MC3T3-E1 pre-osteoblasts. Additionally, SS-Ex upregulated osteogenic genes including runt-related transcription factor 2, osterix, Ocn , osteopontin, Alp, and Col1a1. Whereas mechanistically, SS-Ex downregulated the expression of dickkopf-related protein 1, a negative regulator of the wingless-type MMTV integration site (Wnt)/β-Catenin pathway, thereby activating Wnt3a/β-Catenin signaling. Moreover, SS-Ex upregulated the expression of bone morphogenetic protein 2 (Bmp2), further enhancing osteogenic signaling. These findings suggest that SS-Ex promotes osteoblast differentiation, supports linear bone growth via growth plate stimulation, and helps maintain calcium balance, indicating its potential as a natural agent for enhancing bone development during growth.