Lee Kun-Di, Dawson Paul A, Summers Kim M
Mater Research Institute-University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia.
JBMR Plus. 2025 Aug 7;9(10):ziaf130. doi: 10.1093/jbmrpl/ziaf130. eCollection 2025 Oct.
Sulfate plays a critical role in bone health and development. More than 90 sulfate-related genes are highly conserved across mammalian species, but very few of these genes have been linked to adverse bone phenotypes in humans. To extend our knowledge of sulfate-related gene expression dynamics during mineralization, this study leveraged 6 publicly available transcriptomic datasets, covering human osteosarcoma cell line Saos-2 mineralization, 2 mouse calvarial osteoblast mineralization models, vascular smooth muscle cell (VSMC) calcification, and 2 neurogenic heterotopic ossification datasets. We focused on a total of 12 sulfate-related genes that were upregulated during mineralization of Saos-2 cells. Six of these genes (, , , , , and ) were also consistently upregulated during mouse osteoblast and VSMC mineralization. Additionally, 3 genes (, , and ) were upregulated in Saos-2 mineralization but downregulated in mouse primary osteoblasts. , , and were unchanged in the mouse primary cell models. , , , , and also increased in models of heterotopic ossification. We have now identified several genes (, , , , , , and ) that have not previously been considered for adverse bone conditions in humans, suggesting that additional sulfate biology genes may be linked with human skeletal conditions. Network analysis showed large co-expression clusters of genes, including sulfate biology and bone genes, that were upregulated across the calcification time courses. Gene ontology term enrichment analysis demonstrated significant enrichment in terms associated with mineralization, including ossification, bone mineralization, cartilage development, and extracellular matrix organization for these clusters of genes. This study provides a collated list of sulfate-related genes and networks that are associated with mineralization, which will facilitate future functional studies of sulfation pathways associated with bone pathology.
硫酸盐在骨骼健康与发育中起着关键作用。超过90个与硫酸盐相关的基因在哺乳动物物种中高度保守，但这些基因中很少有与人类不良骨表型相关联的。为了扩展我们对矿化过程中硫酸盐相关基因表达动态的认识，本研究利用了6个公开可用的转录组数据集，涵盖人类骨肉瘤细胞系Saos-2矿化、2个小鼠颅骨成骨细胞矿化模型、血管平滑肌细胞（VSMC）钙化以及2个神经源性异位骨化数据集。我们重点关注了在Saos-2细胞矿化过程中上调的总共12个与硫酸盐相关的基因。其中6个基因（、、、、、和）在小鼠成骨细胞和VSMC矿化过程中也持续上调。此外，3个基因（、和）在Saos-2矿化过程中上调，但在小鼠原代成骨细胞中下调。、、和在小鼠原代细胞模型中未发生变化。、、、和在异位骨化模型中也有所增加。我们现已鉴定出几个以前未被考虑与人类不良骨状况相关的基因（、、、、、和），这表明可能有更多的硫酸盐生物学基因与人类骨骼状况相关联。网络分析显示了大量基因共表达簇，包括硫酸盐生物学和骨骼基因，这些基因在钙化时间进程中均上调。基因本体术语富集分析表明，这些基因簇在与矿化相关的术语中显著富集，包括骨化、骨矿化、软骨发育和细胞外基质组织。本研究提供了一份与矿化相关的硫酸盐相关基因和网络的整理清单，这将有助于未来对与骨病理学相关的硫酸化途径进行功能研究。
