Dcstamp-KO Mouse

DCSTAMP, also known as TM7SF4, is a gene encoding dendritic cell-specific transmembrane protein. It plays a crucial role in osteoclast differentiation, especially in the cell-cell fusion process, which is essential for the formation of multinucleated osteoclasts. The gene is associated with pathways such as NF-κB and NFATc1, which are also involved in osteoclast-related functions [1,3,4]. Understanding DCSTAMP is of great significance for studying bone-related biological processes and diseases.

In multiple studies, substances like aconine, artesunate, and matrix-bound nanovesicles have been shown to inhibit osteoclast differentiation and activity by suppressing DC-STAMP expression. For example, aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression [1]. Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca2 +-NFATc1 signaling pathway, along with inhibiting DC-STAMP expression [3]. Matrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis by suppressing the NF-κB signaling pathway and downstream DC-STAMP expression [4]. Also, in a study on familial Paget's disease of bone, a c.1189C>T p.L397F variant in DC-STAMP was identified, but it was concluded that genetic variation in DCSTAMP is not a significant predisposing factor in that specific cohort [2].

In conclusion, DCSTAMP is a key regulator in osteoclast differentiation, particularly in cell-cell fusion. Research on substances affecting DC-STAMP expression and genetic variants in DCSTAMP has provided insights into its role in bone-related diseases such as osteoclast-mediated bone resorption disorders and Paget's disease of bone. These findings contribute to understanding the biological mechanisms underlying these diseases and may potentially lead to new therapeutic strategies.

References:

1. Zeng, Xiang-zhou, He, Long-gang, Wang, Song, Li, Xiao-juan, Liu, Shu-wen. 2015. Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression. In Acta pharmacologica Sinica, 37, 255-63. doi:10.1038/aps.2015.85. https://pubmed.ncbi.nlm.nih.gov/26592521/

2. Sultana, M A, Pavlos, N J, Ward, Lynley, Walsh, J P, Rea, S L. 2019. Targeted sequencing of DCSTAMP in familial Paget's disease of bone. In Bone reports, 10, 100198. doi:10.1016/j.bonr.2019.100198. https://pubmed.ncbi.nlm.nih.gov/30886882/

3. Zeng, Xiang-Zhou, Zhang, Yue-Yang, Yang, Qin, Liu, Shu-Wen, Li, Xiao-Juan. 2019. Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca2+-NFATc1 signaling pathway. In Acta pharmacologica Sinica, 41, 229-236. doi:10.1038/s41401-019-0289-6. https://pubmed.ncbi.nlm.nih.gov/31431733/

4. Liao, Runzhi, Dewey, Marley J, Rong, Jiayang, Hussey, George S, Badylak, Stephen F. 2024. Matrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis. In Science advances, 10, eadn1852. doi:10.1126/sciadv.adn1852. https://pubmed.ncbi.nlm.nih.gov/39423278/