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Bone. 2015 Sep;78:150-64. doi: 10.1016/j.bone.2015.05.007. Epub 2015 May 9.

Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein.

Author information

1
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), 9000 Rockville Pike, 4120 Building 50, Bethesda, MD 20892, USA. Electronic address: brian.foster@nih.gov.
2
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), 9000 Rockville Pike, 4120 Building 50, Bethesda, MD 20892, USA. Electronic address: fnu.aomin@nih.gov.
3
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), 9000 Rockville Pike, 4120 Building 50, Bethesda, MD 20892, USA. Electronic address: chelseawilloughby15@gmail.com.
4
Biomedical Engineering Program, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada. Electronic address: yosoenjay@uwo.ca.
5
Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada. Electronic address: eholm@uwo.ca.
6
Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA. Electronic address: lukashoval@hss.edu.
7
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), 9000 Rockville Pike, 4120 Building 50, Bethesda, MD 20892, USA. Electronic address: anne.tran2@nih.gov.
8
Department of Vertebrate Zoology, National Museum of Natural History, Smithsonian Institution, Washington, DC, USA. Electronic address: helen.wimer@nih.gov.
9
Office of Research Services, Division of Veterinary Resources, National Institutes of Health (NIH), 9000 Rockville Pike, 112 Building 28A, MSC 5230, Bethesda, MD 20892, USA. Electronic address: patricia.zerfas@nih.gov.
10
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), 9000 Rockville Pike, 4120 Building 50, Bethesda, MD 20892, USA; Department of Prosthodontics and Periodontics, Division of Periodontics, School of Dentistry, Campinas State University, Piracicaba, SP 13414-903, Brazil. Electronic address: nociti@unicamp.br.
11
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), 9000 Rockville Pike, 4120 Building 50, Bethesda, MD 20892, USA; Department of Pediatric Dentistry, School of Dentistry, Campinas State University, Piracicaba, SP 13414-903, Brazil. Electronic address: kamilark@yahoo.com.br.
12
Institute of Biomaterials and Biomedical Engineering, University of Toronto, 320A Mining Building, Toronto, ON M5S 3G9, Canada. Electronic address: bryan.quan@utoronto.ca.
13
Institute of Biomaterials and Biomedical Engineering, University of Toronto, 320A Mining Building, Toronto, ON M5S 3G9, Canada; Department of Materials Science and Engineering, University of Toronto, Toronto, ON, Canada; Faculty of Dentistry, University of Toronto, Toronto, ON, Canada. Electronic address: eli.sone@utotonto.ca.
14
Biomedical Engineering Program, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; School of Dentistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada. Electronic address: hagoldbe@uwo.ca.
15
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), 9000 Rockville Pike, 4120 Building 50, Bethesda, MD 20892, USA. Electronic address: Martha.somerman@nih.gov.

Abstract

Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp(-/-) mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp(-/-) mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp(-/-) mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp(-/-) mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in endochondral ossification in the cranial base, and craniofacial morphology was unaffected in Bsp(-/-) mice. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp(-/-) molar teeth. Dissimilar effects of loss of BSP on mineralization of dental and craniofacial tissues suggest local differences in the role of BSP and/or yet to be defined interactions with site-specific factors.

KEYWORDS:

Bone; Cartilage; Cementum; Dentin; Extracellular matrix; Mineralization

PMID:
25963390
PMCID:
PMC4466207
DOI:
10.1016/j.bone.2015.05.007
[Indexed for MEDLINE]
Free PMC Article

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