title: Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model.
abstract: Understanding periodontal ligament (PDL) biology and developing an effective treatment for bone and PDL damage due to periodontitis have been long-standing aims in dental medicine. Here, we first demonstrated by cell lineage tracing and mineral double-labeling approaches that murine PDL progenitor cells display a 2- and 3-fold higher mineral deposition rate than the periosteum and endosteum at the age of 4 weeks, respectively. We next proved that the pathologic changes in osteocytes (Ocys; changes from a spindle shape to round shape with a >50% reduction in the dendrite number/length, and an increase in SOST) are the key pathologic factors responsible for bone and PDL damage in periostin-null mice (a periodontitis animal model) using a newly developed 3-dimensional FITC-Imaris technique. Importantly, we proved that deleting the Sost gene (a potent inhibitor of WNT signaling) or blocking sclerostin function by using the mAb in this periodontitis model significantly restores bone and PDL defects (n = 4-5; P < 0.05). Together, identification of the key contribution of the PDL in normal alveolar bone formation, the pathologic changes of the Ocys in periodontitis bone loss, and the novel link between sclerostin and Wnt signaling in the PDL will aid future drug development in the treatment of patients with periodontitis.
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
authors.forename: Yinshi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Han
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA sunita.ho@ucsf.edu jfeng@bcd.tamhsc.edu.
authors.forename: Sunita P
authors.initials: SP
authors.lastname: Ho
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Harris
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Cao
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
authors.forename: Aris N
authors.initials: AN
authors.lastname: Economides
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
authors.forename: Huazhu
authors.initials: H
authors.lastname: Ke
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: *Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA sunita.ho@ucsf.edu jfeng@bcd.tamhsc.edu.
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D016301:Alveolar Bone Loss / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D000818:Animals; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics; D019070:Cell Lineage; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010011:Osteocytes / Q000473:pathology; D010513:Periodontal Ligament / Q000473:pathology; D010518:Periodontitis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D010641:Phenotype; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C082838:Postn protein, mouse; C486030:Sost protein, mouse; D003094:Collagen
keywords: PDL; alveolar bone; periostin