FGFR3在软骨发育与稳态维持中的作用与机制研究-科学（野战外科）专业毕业论文.docx

第三军医大学博士学位论文TD 第三军医大学博士学位论文 TD Thanatophoric dysplasia 致死性骨发育不全 TGF·p Transforming growth factor-beta 转化生长因子一p TM Tamoxifen 他莫昔芬 TMJ Temporomandibular joint 颞下颌关节 TRAP Tartrate·resistant acid phosphatase 抗酒石酸酸性磷酸酶 2 万方数据 第三军医大学博士学位论文Th 第三军医大学博士学位论文 Th q rolesdies andan mechanismmecllanlsms of FGFR3 inn bothDoth cartilage development and homeostasis Abstract Fibroblast growth factor receptor(FGFR)3，as a transmembrane receptor,serves essential roles in the early stages of cartilage development．Patients with activating FGFR3 mutations exhibit skeletal dysplasias characterized by short stature including achondroplasia(ACH， OMIM 1 00800)，thanatophoric dysplasia I／II(TD I，OMIM 1 87600 and TD II，OMIM 1 8760 1)，hypochondroplasia(OMIM 1 46000)，and severe ACH with developmental delay with acanthosis nigricans(SADDAN，OMIM 1 87600)．In contrast，a loss-of-function mutation in FGFR3 in humans causes camptodactyly,tall stature，and hearing loss(CATSHL) syndrome(OMIM 6 1 0474)．Thus，FGFR3 is considered to negatively regulate endochondral bone growth during cartilage development，including the proliferation and differentiation of chondrocytes．However,the role and mechanism of FGFR3 in other skeletal diseases remain largely unknown． Benign cartilaginous tumors，including osteochondroma and enchondroma，are the most frequently primary tumors affect skeletal system．Cartilaginous tumors are frequently developed around growth plates during skeleton development，indicating that they may be resulted from disordered endochondrial bone growth．Multiple cartilaginous tumors Can be found in several hereditary diseases，such as hereditary multiple exostoses syndrome(HME， also named hereditary multiple osteochondromas，OMIM 1 33700)，enchondromatosis(oilier diseases and Maffucci syndrome，OMIM 1 66000)and metachondromatosis(MC，OMIM 156250)，which are caused by mutations in the genes，including EXTl／2，PTPNll，PTHRl， IDHl／2．Interestingly,most genes involved in the development of benign cartilaginous tumors a