Matrix Vesicle‐Associated SMS2 as a Novel Mediator of Biomineralization
8 affiliations
- 1Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden
- 2Astrid Lindgren Children's hospital Stockholm Sweden
- 3Folkhälsan Institute of Genetics Folkhälsan Research Center Helsinki Finland
- 4Research Program for Clinical and Molecular Metabolism Faculty of Medicine University of Helsinki Helsinki Finland
- 5Children's Hospital University of Helsinki and Helsinki University Hospital Helsinki Finland
- 6Department of Molecular Medicine and Surgery Karolinska Institutet and Clinical Genetics Karolinska University Laboratory Karolinska University Hospital Stockholm Sweden
- 7Molecular Cell Biology Section Department of Biology/Chemistry Osnabrück University Osnabrück Germany
- 8Center for Cellular Nanoanalytics Osnabrück University Osnabrück Germany
Abstract
SGMS2, a gene encoding plasma membrane‐resident sphingomyelin synthase 2, SMS2, has emerged as an important determinant of skeletal ossification. Heterozygous SGMS2 variants are associated with a broad spectrum of bone phenotypes, ranging from rickets‐like deformities in childhood to early‐onset osteoporosis, implicating SMS2 in mineralization while the underlying mechanisms are incompletely resolved. As SMS2 activity alters the balance of membrane lipids such as ceramide and sphingomyelin, the effects of SMS2 dysfunction on the skeleton are likely to be multifactorial and distributed across multiple cell types and subcellular compartments. Our recent work has identified SMS2 as a key component of growth plate‐derived matrix vesicles, nanoscale membrane‐bound particles released by skeletal cells that nucleate mineral deposition. Consistent with a functional role in this compartment, inhibition of SMS2 reduced the mineralization capacity of isolated matrix vesicles ex vivo. Collectively, these observations suggest that SMS2 contributes directly to biomineralization within matrix vesicles. Here, we place this emerging finding in the broader context of skeletal biology, disease mechanism, and therapeutic potential.
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BibTeX
@article{newton2026matrix,
title = {{Matrix Vesicle‐Associated SMS2 as a Novel Mediator of Biomineralization}},
author = {Phillip T. Newton and Mathieu Y. Brunet and Jose G. Marchan‐Alvarez and Outi Mäkitie and Joost C. M. Holthuis},
journal = {Journal of Extracellular Biology},
year = {2026},
month = nov,
doi = {10.1002/jex2.70199},
url = {https://doi.org/10.1002/jex2.70199},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Matrix Vesicle‐Associated SMS2 as a Novel Mediator of Biomineralization
AU - Phillip T. Newton
AU - Mathieu Y. Brunet
AU - Jose G. Marchan‐Alvarez
AU - Outi Mäkitie
AU - Joost C. M. Holthuis
PY - 2026
DA - 2026/11/03
JO - Journal of Extracellular Biology
DO - 10.1002/jex2.70199
UR - https://doi.org/10.1002/jex2.70199
AB - SGMS2, a gene encoding plasma membrane‐resident sphingomyelin synthase 2, SMS2, has emerged as an important determinant of skeletal ossification. Heterozygous SGMS2 variants are associated with a broad spectrum of bone phenotypes, ranging from rickets‐like deformities in childhood to early‐onset osteoporosis, implicating SMS2 in mineralization while the underlying mechanisms are incompletely resolved. As SMS2 activity alters the balance of membrane lipids such as ceramide and sphingomyelin, the effects of SMS2 dysfunction on the skeleton are likely to be multifactorial and distributed across multiple cell types and subcellular compartments. Our recent work has identified SMS2 as a key component of growth plate‐derived matrix vesicles, nanoscale membrane‐bound particles released by skeletal cells that nucleate mineral deposition. Consistent with a functional role in this compartment, inhibition of SMS2 reduced the mineralization capacity of isolated matrix vesicles ex vivo. Collectively, these observations suggest that SMS2 contributes directly to biomineralization within matrix vesicles. Here, we place this emerging finding in the broader context of skeletal biology, disease mechanism, and therapeutic potential.
SN - 2768-2811
ER -