Levo‐Tryptophan Promotes Osteogenesis Through Calcium‐Sensing Receptor

• 出版年: FASEB BioAdvances
• 主要な著者: Peiran Li, Yanxi Li, Xuejiu Wang, Zhipeng Fan
• フォーマット: 論文
• 言語: 英語
• 出版事項: Wiley 2025-08-01
• 主題: calcium‐sensing receptor; focal adhesion; Levo‐tryptophan; osteoblasts; osteogenesis
• オンライン･アクセス: https://doi.org/10.1096/fba.2025-00130

ABSTRACT Previous studies reported the pro‐osteogenic ability of L‐Tryptophan (L‐Trp) and Calcium‐Sensing RCeceptor (CaSR) respectively. Recent researchers found L‐Trp could activate CaSR. Therefore, this study investigated the osteogenic mechanisms of L‐Trp through CaSR activation. Using in vivo and in vitro models, we evaluated L‐Trp's effects on bone formation and osteoblast activity. Levo‐Trp solution was injected into the temporomandibular joint of 3‐week‐old mice, and the mandibular development was observed by Micro‐CT at 6 weeks of age. The pre‐osteoblast cell line MC3T3‐E1 cells were stimulated by L‐Trp in vitro, and their proliferation, migration, and osteogenic ability were detected by CCK8 assay, alizarin red staining, etc. Transcriptome sequencing was used to investigate the underlying mechanism of L‐Trp stimulation and validated by qPCR and Western blot analyses. Local injection of 0.5% L‐Trp in juvenile mice significantly increased mandibular bone mineral density. In vitro, L‐Trp enhanced MC3T3‐E1 pre‐osteoblast proliferation, migration, and differentiation, with upregulated osteogenic markers (Runx2, Sp7, Alp) and mineralization. CaSR antagonism (NPS‐2143) abolished these effects, confirming CaSR's pivotal role. Transcriptome sequencing revealed L‐Trp activation of the focal adhesion pathway, characterized by increased Ptk2, Rhoa, Itga11, and Clec11a expression. These findings established L‐Trp as a CaSR‐dependent osteogenic enhancer, mediated via the focal adhesion pathway.