Periostin splice variants affect craniofacial growth by influencing chondrocyte hypertrophy
Periostin splice variants affect craniofacial growth by influencing chondrocyte hypertrophy
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DOI：
10.1007/s00774-023-01409-y
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发表时间：
2023-03-01
影响因子：
3.3
通讯作者：
Ono，Takashi
中科院分区：
文献类型：
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作者：
Ishihara，Seiko;Usumi-Fujita，Risa;Ono，Takashi
骨膜蛋白是一种细胞外基质蛋白，在成骨过程中起重要作用，也被认为激活了几种有助于软骨形成的信号。骨膜蛋白敲除小鼠中骨膜蛋白的缺乏导致几种疾病，例如颅缝早闭和骨膜炎。有几种剪接变异体在心脏病和心肌梗死中具有不同的作用。然而，很少有人知道每一个变异的作用，软骨形成，其次是骨形成。因此，本研究的目的是调查的作用，在颅面区域的软骨分化和骨形成的几个变种。骨膜蛋白剪接变体包括全长变体（对照）、缺少外显子17的变体（Δ Ex 17）、缺少外显子21的变体（Δ Ex 21）、而另一种变体同时缺乏外显子17和21 * 材料和方法我们使用C56 BL 6/N小鼠（n = 6）作为野生型（对照）* 和三种变异型小鼠（每种n = 6）以在形态学和组织学上鉴定每种变体的作用。显微计算机断层扫描显示，与对照组相比，Δ Ex 17 s、Δ Ex 21 s和Δ Ex 17和21 s的颅面骨骼较小，尤其是下颌骨。因此，我们，专注于下颌髁状突。ResultsThe最独特的组织学观察是，每一个缺陷的小鼠似乎有更多的肥大软骨细胞比对照组。实时荧光定量PCR显示了各组间的差异。此外，骨膜蛋白中缺乏外显子17或外显子21导致软骨细胞分化不足，并呈现在一个小型的颅面skeleton.DiscussionTherefore，这些研究结果表明，每个变体在软骨细胞肥大中具有重要作用，导致抑制骨形成。
IntroductionPeriostin, an extracellular matrix protein, plays an important role in osteogenesis and is also known to activate several signals that contribute to chondrogenesis. The absence of periostin in periostin knockout mice leads to several disorders such as craniosynostosis and periostitis. There are several splice variants with different roles in heart disease and myocardial infarction. However, little is known about each variant’s role in chondrogenesis, followed by bone formation. Therefore, the aim of this study is to investigate the role of several variants in chondrogenesis differentiation and bone formation in the craniofacial region. Periostin splice variants included a full-length variant (Control), a variant lacking exon 17 (ΔEx17), a variant lacking exon 21 (ΔEx21), and another variant lacking both exon 17 and 21 ***(ΔEx17&21).Materials and MethodsWe used C56BL6/N mice (n = 6) for the wild type (Control)*** and the three variant type mice (n = 6 each) to identify the effect of each variant morphologically and histologically. Micro-computed tomography demonstrated a smaller craniofacial skeleton in ΔEx17s, ΔEx21s, and ΔEx17&21s compared to Controls, especially the mandibular bone. We, thus, focused on the mandibular condyle.ResultsThe most distinctive histological observation was that each defected mouse appeared to have more hypertrophic chondrocytes than Controls. Real-time PCR demonstrated the differences among the group. Moreover, the lack of exon 17 or exon 21 in periostin leads to inadequate chondrocyte differentiation and presents in a diminutive craniofacial skeleton.DiscussionTherefore, these findings suggested that each variant has a significant role in chondrocyte hypertrophy, leading to suppression of bone formation.