دورية أكاديمية
أعرض في EDS

Functional defects in cementoblasts with disrupted bone sialoprotein functional domains, in vitro.

التفاصيل البيبلوغرافية
العنوان: Functional defects in cementoblasts with disrupted bone sialoprotein functional domains, in vitro.
المؤلفون: Chavez MB; Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA; College of Dentistry, University of Iowa, Iowa City, IA, USA., Tan MH; Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA., Kolli TN; Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA., Andras NL; Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA., Foster BL; Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA. Electronic address: foster.1004@osu.edu.
المصدر: Bone [Bone] 2024 Feb; Vol. 179, pp. 116961. Date of Electronic Publication: 2023 Nov 10.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 8504048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2763 (Electronic) Linking ISSN: 18732763 NLM ISO Abbreviation: Bone Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Elsevier Science
Original Publication: Elmsford, NY : Pergamon Press, c1985-
مواضيع طبية MeSH: Dental Cementum*/metabolism , Extracellular Matrix Proteins*, Mice ; Animals ; Integrin-Binding Sialoprotein/genetics ; Integrin-Binding Sialoprotein/metabolism ; Collagen ; Integrins ; Oligopeptides
مستخلص: Bone sialoprotein (BSP) is a multifunctional extracellular matrix (ECM) protein present in bone and cementum. Global in vivo ablation of BSP leads to bone mineralization defects, lack of acellular cementum, and periodontal breakdown. BSP harbors three main functional domains: N-terminal collagen-binding domain, hydroxyapatite-nucleating domain, and C-terminal RGD integrin-binding signaling domain. How each of these domains contributes to BSP function(s) is not understood. We hypothesized that collagen-binding and RGD domains play distinct roles in cementoblast functions. Three CRISPR/Cas9 gene-edited cell lines were derived from control wild-type (WT) OCCM.30 murine immortalized cementoblasts: 1) deletion of the N-terminus of BSP after signal peptide, including entire collagen binding domain (Ibsp ∆N-Term ); 2) deletion of exon 4 (majority of collagen-binding domain; Ibsp ∆Ex4 ); and 3) deletion of C-terminus of BSP including the integrin binding RGD domain (Ibsp ∆C-Term ). Compared to WT, Ibsp ∆Ex4 and Ibsp ∆C-Term cell lines showed reduced BSP secretion, in vitro. Abnormal cell morphology was observed in all mutant cell lines, with Ibsp ∆C-Term showing highly disorganized cytoskeleton. All mutant cell lines showed significantly lower cell proliferation compared to WT at all timepoints. Ibsp ∆N-Term cells showed reduced cell migration by 24 h. All mutants exhibited over 50 % significant reduced mineralization at days 6 and 10. While WT cells were largely unaffected by seeding density, mutant cells failed to mineralize at lower cell density. Mutant cell lines diverged from WT and from each other by dysregulated expression in 23 genes involved in mineralization, ECM, and cell signaling. In summary, disabling BSP functional domains led to profound and distinct changes in cementoblast cell functions, especially dysregulated gene expression and reduced mineralization, in a way did not align with a straightforward narrative where each functional domain caused specific, expected differences. Instead, the study uncovered a significant level of complexity in how different mutant forms of BSP affected cell functions, in vitro.
Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
References: Cell Death Discov. 2023 Apr 10;9(1):119. (PMID: 37037822)
J Dent Res. 2015 Sep;94(9):1276-85. (PMID: 26130257)
Connect Tissue Res. 2003;44 Suppl 1:97-102. (PMID: 12952181)
Connect Tissue Res. 2003;44 Suppl 1:33-40. (PMID: 12952171)
Bone. 2015 Sep;78:150-64. (PMID: 25963390)
PLoS One. 2015 Feb 24;10(2):e0117402. (PMID: 25710686)
J Periodontol. 2015 Feb;86(2):319-26. (PMID: 25345341)
J Periodontol. 2000 Jan;71(1):63-72. (PMID: 10695940)
Cell. 2002 Sep 20;110(6):673-87. (PMID: 12297042)
Osteoporos Int. 2019 Sep;30(9):1873-1885. (PMID: 31338519)
Ann Anat. 2023 Aug;249:152102. (PMID: 37150306)
J Biol Chem. 2005 Apr 8;280(14):13487-92. (PMID: 15703183)
J Exp Med. 2008 May 12;205(5):1145-53. (PMID: 18458111)
Bone. 2007 Sep;41(3):462-73. (PMID: 17572166)
Bone. 2015 Feb;71:145-54. (PMID: 25464126)
J Dent Res. 2021 Aug;100(9):993-1001. (PMID: 33840251)
Bone. 2017 Dec;105:134-147. (PMID: 28866368)
J Dent Res. 2023 Feb;102(2):187-196. (PMID: 36377066)
J Dent Res. 2018 Jul;97(7):803-809. (PMID: 29420105)
Crit Rev Oral Biol Med. 1999;10(1):79-98. (PMID: 10759428)
J Dent Res. 2022 Sep;101(10):1238-1247. (PMID: 35686360)
Biochem J. 2010 May 27;428(3):385-95. (PMID: 20377527)
Bone. 2019 May;122:176-183. (PMID: 30408613)
Nat Cell Biol. 2019 Feb;21(2):122-132. (PMID: 30602723)
Matrix Biol. 2008 Sep;27(7):600-8. (PMID: 18620053)
J Dent Res. 2013 Feb;92(2):166-72. (PMID: 23183644)
J Periodontal Res. 2023 Apr;58(2):414-421. (PMID: 36691857)
Cells Tissues Organs. 2009;189(1-4):138-43. (PMID: 18728350)
معلومات مُعتمدة: F30 DE030358 United States DE NIDCR NIH HHS; F30 DE032897 United States DE NIDCR NIH HHS; R01 DE027639 United States DE NIDCR NIH HHS; T32 DE014320 United States DE NIDCR NIH HHS
فهرسة مساهمة: Keywords: Bone biology; Bone remodeling/regeneration; Extracellular matrix (ECM); Mineralized tissue/development; Osteoblast(s)
المشرفين على المادة: 0 (Integrin-Binding Sialoprotein)
0 (Extracellular Matrix Proteins)
9007-34-5 (Collagen)
0 (Integrins)
0 (Oligopeptides)
تواريخ الأحداث: Date Created: 20231111 Date Completed: 20240105 Latest Revision: 20240304
رمز التحديث: 20240305
مُعرف محوري في PubMed: PMC10841848
DOI: 10.1016/j.bone.2023.116961
PMID: 37951522
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2763
DOI:10.1016/j.bone.2023.116961