title: Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects.
abstract: During endochondral ossification, chondrocytes embed themselves in a proteoglycan-rich matrix during the proliferation-maturation transition. Accumulating evidence shows that proteoglycans are essential components for chondrocyte proliferation and differentiation. When we conditionally inactivated FAM20B (Family with sequence similarity 20 member-B), which is a newly identified xylose kinase essential for glycosaminoglycan (GAG) formation on the protein core of proteoglycans, from the dental mesenchyme using Osr2-Cre, which is also strongly expressed in joint cartilage, we found chondrosarcoma in the knee joint and remarkable defects of postnatal ossification in the long bones. Mechanistic analysis revealed that the defects were associated with gain of function in multiple signaling pathways in the epiphyseal chondrocytes, such as those derived by WNT, BMP, and PTHrP/IHH molecules, suggesting that the FAM20B-catalyzed proteoglycans are critical mediators for a signaling balance in the regulatory network controlling chondrocyte differentiation and proliferation. In particular, we demonstrated that the WNT inhibitor was able to rescue part of the bone defects in Osr2-Cre;Fam20B(fl/fl) mice, indicating that FAM20B-catalyzed proteoglycans regulate postnatal endochondral ossification partially through the mediation of WNT signaling.
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, United States of America.|Department of Oral Implantology, Beijing Stomatological Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Pan
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, United States of America.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, United States of America.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, United States of America.
authors.forename: Jingya
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, United States of America.
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, United States of America.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Diagnostic Sciences, Texas A&M University Baylor College of Dentistry, 3302 Gaston Ave, Dallas, TX, United States of America.
authors.forename: Yi-Shing Lisa
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, United States of America.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009999:Ossification, Heterotopic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor); D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C509695:FAM20B protein, mouse; D009363:Neoplasm Proteins; D011506:Proteins; D011509:Proteoglycans; D017853:Phosphotransferases (Alcohol Group Acceptor)