Baddam Pranidhi, Young Daniel, Dunsmore Garett, Nie Chunpeng, Eaton Farah, Elahi Shokrollah, Jovel Juan, Adesida Adetola B, Dufour Antoine, Graf Daniel
School of Dentistry, University of Alberta, Edmonton, AB, Canada.
Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
Front Cell Dev Biol. 2021 Jun 24;9:696545. doi: 10.3389/fcell.2021.696545. eCollection 2021.
The nasal septum cartilage is a specialized hyaline cartilage important for normal midfacial growth. Abnormal midfacial growth is associated with midfacial hypoplasia and nasal septum deviation (NSD). However, the underlying genetics and associated functional consequences of these two anomalies are poorly understood. We have previously shown that loss of Bone Morphogenetic Protein 7 (BMP7) from neural crest (BMP7 ) leads to midfacial hypoplasia and subsequent septum deviation. In this study we elucidate the cellular and molecular abnormalities underlying NSD using comparative gene expression, quantitative proteomics, and immunofluorescence analysis. We show that reduced cartilage growth and septum deviation are associated with acquisition of elastic cartilage markers and share similarities with osteoarthritis (OA) of the knee. The genetic reduction of BMP2 in BMP7 mice was sufficient to rescue NSD and suppress elastic cartilage markers. To our knowledge this investigation provides the first genetic example of an cartilage fate switch showing that this is controlled by the relative balance of BMP2 and BMP7. Cellular and molecular changes similar between NSD and knee OA suggest a related etiology underlying these cartilage abnormalities.
鼻中隔软骨是一种特殊的透明软骨，对正常的面中部生长至关重要。面中部生长异常与面中部发育不全和鼻中隔偏曲（NSD）有关。然而，这两种异常的潜在遗传学及相关功能后果仍知之甚少。我们之前已经表明，神经嵴中骨形态发生蛋白7（BMP7）的缺失（BMP7-/-）会导致面中部发育不全及随后的鼻中隔偏曲。在本研究中，我们使用比较基因表达、定量蛋白质组学和免疫荧光分析来阐明NSD背后的细胞和分子异常。我们表明，软骨生长减少和鼻中隔偏曲与弹性软骨标志物的获得有关，并且与膝关节骨关节炎（OA）有相似之处。BMP7-/-小鼠中BMP2的基因敲低足以挽救NSD并抑制弹性软骨标志物。据我们所知，这项研究提供了软骨命运转换的首个遗传学实例，表明这是由BMP2和BMP7的相对平衡控制的。NSD和膝关节OA之间相似的细胞和分子变化表明这些软骨异常存在相关的病因。
