title: ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.
abstract: Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development.
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: tanyu2048@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: furunqing@sjtu.edu.cn.
authors.forename: Runqing
authors.initials: R
authors.lastname: Fu
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: liujqmj@163.com.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: wyonger@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: wb228@126.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: 179639060@qq.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: nieping1011@sina.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Nie
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: 0412chf@163.com.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: wcums1981@163.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Oral & Cranio-Maxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China. Electronic address: fangbing@sjtu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Fang
mesh_terms: D000072197:ADAM10 Protein / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D000818:Animals; D049109:Cell Proliferation; D019465:Craniofacial Abnormalities / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D008334:Mandible / Q000196:embryology* / Q000378:metabolism; D008437:Maxilla / Q000196:embryology* / Q000378:metabolism; D008445:Maxillofacial Development; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology; D012886:Skull / Q000196:embryology* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse
keywords: ADAM10; Cranial neural crest cells; Intramembranous bone formation; Maxillofacial bone