LI Fangfang,XIE Yangli,HUANG Junlan,et al.Developmental process and expression patterns of fibroblast growth factor receptors in murine meniscus after birth [J].J Third Mil Med Univ,2019,41(07):646-652.

小鼠出生后半月板的发育过程及成纤维细胞生长因子受体的表达模式(/HTML )




Developmental process and expression patterns of fibroblast growth factor receptors in murine meniscus after birth
陆军军医大学(第三军医大学)大坪医院野战外科研究所战创伤康复医学研究室,全军军事训练伤防治与康复实验室, 创伤、烧伤与复合伤国家重点实验室
LI Fangfang XIE Yangli HUANG Junlan ZHANG Ruobin JIANG Wanling ZHANG Dali XU Meng DU Xiaolan CHEN Lin

State Key Laboratory of Trauma, Burns and Combined Injury,  Laboratory for Rehabilitation of Traumatic Injuries, Laboratory for Prevention and Rehabilitation of Military Training Related Injury, Institute of Surgery Research, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China


meniscus development fibroblast growth factor receptors mice  
R322.72; R329.24

目的 观察小鼠出生后半月板发育过程的组织形态学变化及3种成纤维细胞生长因子受体(fibroblast growth factor receptors,FGFRs)的时空表达规律。方法 取材出生后不同年龄(1日龄和1、2、4、6、12周龄)C57BL/6J小鼠膝关节行石蜡切片,藏红固绿染色观察小鼠半月板的结构,用免疫组织化学方法检测小鼠半月板Ⅰ型胶原(type Ⅰ collagen, Col Ⅰ)、Ⅱ型胶原(type Ⅱ collagen, Col Ⅱ)和FGFR1、2、3的表达。结果 小鼠出生后,半月板具有明确的内外侧分区,内侧区富含蛋白聚糖,藏红着色较深,而外侧区藏红着色浅。1周时分区更加明显,内侧区主要表达Ⅱ型胶原,而外侧区主要表达Ⅰ型胶原。出生后2周,半月板中间部分细胞开始肥大化,4周时细胞肥大化进一步加重,到6周时,在半月板前角出现小面积的矿化。12周时,半月板出生后的发育过程基本完成,前角出现类似骨髓腔的结构。整个发育过程,FGFR1、2、3的时空表达模式相似,表现为前角的表达于1~2周时达到高峰,而后逐渐减少(P<0.05),并由内侧区均匀分布逐渐变为表层边缘分布,而后角FGFRs的表达无明显变化。结论 小鼠半月板在出生后的发育过程中,软骨基质、胶原分布以及FGFRs的表达均存在时空特异性规律,提示FGFRs在半月板发育过程中起重要作用。


Objective To observe the developmental process of murine meniscus after birth and investigate the expression patterns of 3 types of fibroblast growth factor receptors (FGFRs) during this process. Methods Mice at different ages (1 d old and 1, 2, 4, 6 and 12 weeks old) were sacrificed and the knee joints were harvested and embedded in paraffin. The sagittal sections of knee joint were stained with Safranin O-fast green to observe the structure of murine meniscus. The expression of type Ⅰ collagen, type Ⅱ collagen, and 3 types of FGFRs were detected by immunohistochemistry. Results At birth, the meniscus exhibited distinguishable inner and outer regions, with  proteoglycan of darker staining rich in the inner region, while the outer region lightly stained. At 1-week age, the inner-outer region was more obvious, and the inner region mainly expressed type Ⅱ   collagen, while the outer region expressed type Ⅰ collagen. At 2 weeks, some cells in the anterior horn became hypertrophied, and the hypertrophy was further aggravated at 4 weeks of age. By 6 weeks, ossification tissues were observed in the anterior horn of the meniscus. At 12 weeks, the meniscal developmental process after birth was basically completed, and mineralized structure resembling bone marrow cavity was found in the anterior horn. The expression of the 3 types of FGFRs had similar spatiotemporal pattern which reached a peak at 1~2 weeks of age and then gradually decreased (P<0.05) with its spatial distribution changing from a uniform distribution to an edged distribution in the inner zone of anterior horn. However, the expression of FGFRs in the posterior horn had no obvious changes. Conclusion During the postnatal development of murine meniscus, the cartilage matrix, collagen distribution and expression patterns of 3 types of FGFRs have spatiotemporal specificity, which suggest that FGFRs play an important role in the meniscal development.


[1]MAKRIS E A, HADIDI P, ATHANASIOU K A. The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration[J]. Biomaterials, 2011, 32(30): 7411-7431. DOI:10.1016/j.biomaterials.2011.06.037.
[2]MCDEVITT C A, WEBBER R J. The ultrastructure and biochemistry of meniscal cartilage[J]. Clin Orthop Relat Res, 1990(252): 8-18. DOI:10.1097/00003086-19900-300000003.
[3]MCNULTY A L, GUILAK F. Mechanobiology of the meniscus[J]. J Biomech, 2015, 48(8): 1469-1478. DOI:10.1016/j.jbiomech.2015.02.008.
[4]ARNOCZKY S P, WARREN R F. Microvasculature of the human meniscus[J]. Am J Sports Med, 1982, 10(2): 90-95. DOI:10.1177/036354658201000205.
[5]ANDERSSONMOLINA H, KARLSSON H, ROCKBORN P. Arthroscopic partial and total meniscectomy[J]. Arthroscopy, 2002, 18(2): 183-189. DOI:10.1053/jars.2002.30435.
[6]ROOS E M, OSTENBERG A, ROOS H, et al. Long-term outcome of meniscectomy: symptoms, function, and performance tests in patients with or without radiographic osteoarthritis compared to matched controls[J]. Osteoarthr Cartil, 2001, 9(4): 316-324. DOI:10.1053/joca.2000.0391.
[7]SIHVONEN R, PAAVOLA M, MALMIVAARA A, et al. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear[J]. N Engl J Med, 2013, 369(26): 2515-2524. DOI:10.1056/NEJMoa1305189.
[8]SANCHEZADAMS J, ATHANASIOU K A. The knee meniscus: a complex tissue of diverse cells[J]. Cel Mol Bioeng, 2009, 2(3): 332-340. DOI:10.1007/s12195-009-0066-6.
[9]SU N, JIN M, CHEN L. Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models[J]. Bone Res, 2014, 2: 14003. DOI:10.1038/boneres.2014.3.
[10]ORNITZ D M, MARIE P J. Fibroblast growth factor signaling in skeletal development and disease[J]. Genes Dev, 2015, 29(14): 1463-1486. DOI:10.1101/gad.266551.115.
[11]VERDONK P C M, FORSYTH R G, WANG J, et al. Characterisation of human knee meniscus cell phenotype[J]. Osteoarthr  Cartil, 2005, 13(7): 548-560. DOI:10.1016/j.joca.2005.01.010.
[12]MELROSE J, SMITH S, CAKE M, et al. Comparative spatial and temporal localisation of perlecan, aggrecan and type Ⅰ, Ⅱ and Ⅳ collagen in the ovine meniscus: an ageing study[J]. Histochem Cell Biol, 2005, 124(3/4): 225-235. DOI:10.1007/s00418-005-0005-0.
[13]FOX A J, BEDI A, RODEO S A. The basic science of human knee menisci: structure, composition, and function[J]. Sports Health, 2012, 4(4): 340-351. DOI:10.1177/1941738111429419.
[14]KREINEST M, REISIG G, STRBEL P, et al. Analysis of gene expression and ultrastructure of stifle menisci from juvenile and adult pigs[J]. Comp Med, 2016, 66(1): 30-40.
[15]GLASS R S, BARNES W M, KELLS D U, et al. Ossicles of knee menisci[J]. Clin Orthop Relat Res, 1975, 111: 163-171. DOI:10.1097/00003086-197509000-00023.
[16]ISEKI S, WILKIE A O, MORRISSKAY G M. Fgfr1 and Fgfr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault[J]. Development, 1999, 126(24): 5611-5620.
[17]苏楠,陈林.FGFG3在骨骼发育和疾病中作用的研究进展[J].国际遗传学杂志,2006,29(3):222-225. DOI:10.3760/cma.j.issn.16734386.2006.03.0157.
SU N,CHEN L. The effect of FGFR3 on skeleton development and disease[J]. Int J Genet,2006, 29(3):222-225. DOI:10.3760/cma.j.issn.16734386.2006.03.0157.
[18]HYDE G, BOOTHANDFORD R P, WALLIS G A. Col2a1 lineage tracing reveals that the meniscus of the knee joint has a complex cellular origin[J]. J Anat, 2008,213(5):531-538.DOI:10.1111/j.1469-7580.2008.00966.x.


 LIU Jian-jun,CAI Wen-qin,LIU Yun-lai,et al.Expression and localization of Dbn1 in the developmental mouse brain[J].J Third Mil Med Univ,2007,29(07):1485.
 Zong Zhaowen,Chen Sixu,Jia Min,et al.Role of Osterix in development of spine in mice[J].J Third Mil Med Univ,2013,35(07):220.
 QIN Wei,YIN Zheng-qin,WENG Chuan-huang,et al.Properties of the postsynaptic currents mediated by NMDA receptors or GABAA receptors recorded in the pyramidal or granular neurons of rat visual cortex[J].J Third Mil Med Univ,2008,30(07):714.
 CHEN Peng-hui,CAI Wen-qin,WANG Li-yan.Postnatal development and perinatal electrophysiological characteristics of oligodendrocyte precursor cell in rats[J].J Third Mil Med Univ,2008,30(07):1783.
 Liu Yunlai,Li Hongli,Sun Yu,et al.Expression of BAT2L protein in developmental brain of rats[J].J Third Mil Med Univ,2010,32(07):922.
 ZHANG Yu-ping,HUANG Qi-lin,ZHAO Cong-min,et al.Myelination of rat brain at different developmental stages[J].J Third Mil Med Univ,2009,31(07):2189.
 Guo Liang,Huang Wei,Xu Pei,et al.Liver X receptor β participates in cell proliferation and fiber formation of radial glial cells in hippocampal dentate gyrus of perinatal mice[J].J Third Mil Med Univ,2011,33(07):2545.

更新日期/Last Update: 2019-04-05