Laboratory of Molecular Signaling, Division of Oral and Systemic Health Sciences, School of Dentistry, UCLA, Los Angeles, CA, USA.
Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
Int J Oral Sci. 2022 May 7;14(1):24. doi: 10.1038/s41368-022-00175-3.
Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects, and complicates dental treatment outcomes. Age-related alveolar bone loss could be attributed to decreased progenitor pool through senescence, imbalance in bone metabolism and bone-fat ratio. Mesenchymal stem cells isolated from oral bones (OMSCs) have distinct lineage propensities and characteristics compared to MSCs from long bones, and are more suited for craniofacial regeneration. However, the effect of epigenetic modifications regulating OMSC differentiation and senescence in aging has not yet been investigated. In this study, we found that the histone demethylase KDM4B plays an essential role in regulating the osteogenesis of OMSCs and oral bone aging. Loss of KDM4B in OMSCs leads to inhibition of osteogenesis. Moreover, KDM4B loss promoted adipogenesis and OMSC senescence which further impairs bone-fat balance in the mandible. Together, our data suggest that KDM4B may underpin the molecular mechanisms of OMSC fate determination and alveolar bone homeostasis in skeletal aging, and present as a promising therapeutic target for addressing craniofacial skeletal defects associated with age-related deteriorations.
颅面骨骼老化显著损害了创伤诱导的骨缺损的修复和再生，并使牙科治疗结果复杂化。与长骨来源的间充质干细胞（MSCs）相比，源自口腔骨（OMSCs）的 MSCs 具有独特的谱系倾向和特性，更适合颅面再生。然而，调节 OMSC 分化和衰老的表观遗传修饰在衰老中的作用尚未得到研究。在这项研究中，我们发现组蛋白去甲基酶 KDM4B 在调节 OMSCs 成骨和口腔骨老化中起着至关重要的作用。OMSCs 中 KDM4B 的缺失导致成骨作用受到抑制。此外，KDM4B 的缺失促进了脂肪生成和 OMSC 衰老，从而进一步破坏了下颌骨的骨脂平衡。总之，我们的数据表明，KDM4B 可能是 OMSC 命运决定和骨骼衰老中牙槽骨动态平衡的分子机制的基础，为解决与年龄相关的恶化相关的颅面骨骼缺陷提供了有希望的治疗靶点。
