Center for Craniofacial Research, UTHealth School of Dentistry, Houston, TX, USA.
Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Mol Genet Genomic Med. 2020 Jul;8(7):e1251. doi: 10.1002/mgg3.1251. Epub 2020 Apr 28.
Cartilage oligomeric matrix protein (COMP) is an important extracellular matrix protein primarily functioning in the musculoskeletal tissues and especially endochondral bone growth. Mutations in COMP cause the skeletal dysplasia pseudoachondroplasia (PSACH) that is characterized by short limbs and fingers, joint laxity, and abnormalities but a striking lack of skull and facial abnormalities.
This study examined both mice and humans to determine how mutant-COMP affects face and skull growth.
Mutant COMP (MT-COMP) mice were phenotypically distinct. Snout length and skull height were diminished in MT-COMP mouse and the face more closely resembled younger controls. Three-dimensional facial measurements of PSACH faces showed widely spaced eyes, reduced lower facial height, and decreased nasal protrusion, which correlated with a more juvenile appearing face. Neither MT-COMP mice nor PSACH individuals show midface hypoplasia usually associated with abnormal endochondral bone growth. MT-COMP mice do show delayed endochondral and membranous skull ossification that normalizes with age.
Therefore, mutant-COMP affects both endochondral and intramembranous bones of the skull resulting in a reduction of the nose and lower facial height in mice and humans, in addition to its well-defined role in the growth plate chondrocytes.
软骨寡聚基质蛋白（COMP）是一种重要的细胞外基质蛋白，主要在肌肉骨骼组织中发挥作用，特别是在骺软骨生长中。COMP 的突变导致假性软骨发育不全（PSACH），其特征为四肢和手指短小、关节松弛和异常，但明显缺乏颅骨和面部异常。
本研究通过检查老鼠和人类，确定突变型 COMP 如何影响面部和颅骨生长。
突变型 COMP（MT-COMP）老鼠表现出明显的表型差异。MT-COMP 老鼠的鼻长和颅高降低，且面部更类似于年轻的对照。PSACH 面部的三维面部测量显示眼睛间距宽、下颜面高度降低和鼻突出减少，这与更年轻的面部外观相关。MT-COMP 老鼠和 PSACH 个体均未出现与异常骺软骨生长相关的中面部发育不全。MT-COMP 老鼠确实显示出延迟的软骨内和膜内颅骨骨化，随着年龄的增长而正常化。
因此，突变型 COMP 不仅在生长板软骨细胞中发挥其明确作用，还影响颅骨的软骨内和膜内骨骼，导致老鼠和人类的鼻子和下颜面高度降低。
