The development of the skeleton is regulated by numerous signaling molecules expressed in epiphyseal cartilage controlling both chondrogenesis and osteogenesis such as fibroblast growth factor receptors (FGFRs). In order to explore the important effect of fibroblast growth factor receptor 2 (FGFR2) in the process of mandibular condylar growth, we introduced gain-of-function Fgfr2+/S252W mice, and investigated mandibular condylar morphology by means of safranin-o/fast green staining at the stage of 1 week, 3 weeks and 6 weeks. The mutant mice displayed narrower width of the mandibular condylar growth plate, stronger stainings of trabecular bone at the stage of 1 week, 3 weeks and 6 weeks and faster degradation of the calcified cartilage cell layer at the stage of 6 weeks. We also assessed the expression of type X collagen (Col X) in mandibular condyle at the stage of 3 weeks by immunohistochemical staining and real-time PCR. The results showed that Col X was increased in the mutant mice. In conclusion, the gain-of-function mutation in FGFR2 resulted in histopathological abnormalities and development deformity of mandibular condyle cartilage in mice, which inhibited endochondral bone formation.
Xin Liang, Bo Zhang, Ping Liu, Tujun Weng, Li Zhang, Longzhu He, Fangfei Li, Chen Qu, Ping Wang
. A gain-of-function mutation in FGFR2 influences mandibular condylar development on mice[J]. Hereditas(Beijing), 2015
, 37(6)
: 561
-567
.
DOI: 10.16288/j.yczz.14-370
[1] Martín AE, del R Pani M, Holgado NR, López Miranda LI, Meheris HE, Garat JA. Facial development disorders due to inhibition to endochondral ossification of mandibular condyle process caused by malnutrition. Angle Orthod , 2014, 84(3): 473-478.
[2] Xie YL, Zhou SR, Chen HG, Du XL, Chen L. Recent research on the growth plate: Advances in fibroblast growth factor signaling in growth plate development and disorders. J Mol Endocrinol , 2014, 53(1): T11-T34.
[3] Itoh N, Ornitz DM. Evolution of the Fgf and Fgfr gene families. Trends Genet , 2004, 20(11): 563-569.
[4] Lajeunie E, Cameron R, El Ghouzzi V, De Parseval N, Journeau P, Gonzales M, Delezoide AL, Bonaventure J, Le Merrer M, Renier D. Clinical variability in patients with Apert’s syndrome. J Neurosurg , 1999, 90(3): 443-447.
[5] Yu K, Ornitz DM. Uncoupling fibroblast growth factor receptor 2 ligand binding specificity leads to Apert syndrome-likephenotypes. Proc Natl Acad Sci USA , 2001, 98(7): 3641-3643.
[6] Wang YL, Xiao R, Yang F, Karim BO, Iacovelli AJ, Cai JL, Lerner CP, Richtsmeier JT, Leszl JM, Hill CA, Yu K, Ornitz DM, Elisseeff J, Huso DL, Jabs EW. Abnormalities in cartilage and bone development in the Apert syndrome FGFR2 +/S252W mouse. Development , 2005, 132(15): 3537- 3548.
[7] Chen L, Li D, Li CL, Engel A, Deng CX. A Ser 252 Trp substitution in mouse fibroblast growth factor receptor 2(Fgfr2) result in craniosynostosis. Bone , 2003, 33(2): 169-178.
[8] Kronenbcrg HM. Developmental regulation of the growth plate. Nature , 2003, 423(6937): 332-336.
[9] Zuscik MJ, Hilton MJ, Zhang XP, Chen D, O’Keefe RJ. Regulation of chondrogenesis and chondrocyte differentiation by stress. J Clin Invest , 2008, 118(2): 429-438.
[10] 谷志远, 胡莹, 张银凯, 冯剑颖, 胡济安. 髁突软骨的细胞分层及其功能研究. 中华口腔医学杂志, 2004, 39(5): 366.
[11] Schmid TM, Linsenmayer TF. Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues. J Cell Biol , 1985, 100(2): 598-605.
[12] Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev , 2002, 16(12): 1446-1465.
[13] Yasuda T, Nah HD, Laurita J, Kinumatsu T, Shibukawa Y, Shibutani T, Minugh-Purvis N, Pacifici M, Koyama E. Muenke syndrome mutation, fgfr3 P244R , causes TMJ defects. J Dent Res , 2012, 91(7): 683-689.
[14] Lin Y, Ai SM, Chen C, Liu XL, Luo LX, Ye SB, Liang XW, Zhu Y, Yang HS, Liu YZ. Ala344Pro mutation in the Fgfr 2 gene and related clinical findings in one Chinese family with Crouzon syndrome. Mol Vis , 2012, 18: 1278-1282.
[15] Lajeunie E, Ma HW, Bonaventure J, Munnich A, Le Merrer M, Renier D. FGFR2 mutations in Pfeiffer syndrome. Nat Genet , 1995, 9(2): 108.