Center for Craniofacial Research, Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas.
Dev Dyn. 2019 Mar;248(3):221-232. doi: 10.1002/dvdy.13. Epub 2019 Feb 7.
Interferon regulatory factor 6 (IRF6) plays a critical role in embryonic tissue development, including differentiation of epithelial cells. Besides orofacial clefting due to haploinsufficiency of IRF6, recent human genetic studies indicated that mutations in IRF6 are linked to small mandible and digit abnormalities. The function of IRF6 has been well studied in oral epithelium; however, its role in craniofacial skeletal formation remains unknown. In this study, we investigated the role of Irf6 in craniofacial bone development using comparative analyses between wild-type (WT) and Irf6-null littermate mice.
Immunostaining revealed the expression of IRF6 in hypertrophic chondrocytes, osteocytes, and bone matrix of craniofacial tissues. Histological analysis of Irf6-null mice showed a remarkable reduction in the number of lacunae, embedded osteocytes in matrices, and a reduction in mineralization during bone formation. These abnormalities may explain the decreased craniofacial bone density detected by micro-CT, loss of incisors, and mandibular bone abnormality of Irf6-null mice. To validate the autonomous role of IRF6 in bone, extracted primary osteoblasts from calvarial bone of WT and Irf6-null pups showed no effect on osteoblastic viability and proliferation. However, a reduction in mineralization was detected in Irf6-null cells.
Altogether, these findings suggest an autonomous role of Irf6 in regulating bone differentiation and mineralization. Developmental Dynamics 248:221-232, 2019. © 2019 Wiley Periodicals, Inc.
干扰素调节因子 6（IRF6）在胚胎组织发育中起着关键作用，包括上皮细胞的分化。除了由于 IRF6 的单倍不足引起的口腔面裂外，最近的人类遗传研究表明，IRF6 的突变与小下颌和指骨异常有关。IRF6 的功能已在口腔上皮中得到很好的研究；然而，其在颅面骨骼形成中的作用尚不清楚。在这项研究中，我们使用野生型（WT）和 Irf6 缺失同窝仔鼠之间的比较分析来研究 Irf6 在颅面骨发育中的作用。
免疫染色显示 IRF6 在颅面组织的肥大软骨细胞、骨细胞和骨基质中表达。Irf6 缺失小鼠的组织学分析显示，腔隙数量、嵌入基质中的成骨细胞以及骨形成过程中的矿化减少。这些异常可能解释了微 CT 检测到的颅面骨密度降低、缺失切牙和 Irf6 缺失小鼠下颌骨异常。为了验证 IRF6 在骨骼中的自主作用，从 WT 和 Irf6 缺失幼鼠的颅骨中提取的原代成骨细胞对成骨细胞的活力和增殖没有影响。然而，在 Irf6 缺失细胞中检测到矿化减少。
总之，这些发现表明 Irf6 在调节骨分化和矿化中具有自主作用。发育动力学 248:221-232，2019。© 2019 威利期刊公司
