Aberrant activation of Wnt signaling pathway altered osteocyte mineralization

Yinghong Zhou; Jinying Lin; Jin Shao; Qiliang Zuo; Shengfang Wang; Annalena Wolff; Dung Trung Nguyen; Llew Rintoul; Zhibin Du; Yuantong Gu; Yong Y Peng; John A M Ramshaw; Xing Long; Yin Xiao

doi:10.1016/j.bone.2019.06.027

Aberrant activation of Wnt signaling pathway altered osteocyte mineralization

Bone. 2019 Oct:127:324-333. doi: 10.1016/j.bone.2019.06.027. Epub 2019 Jun 28.

Authors

Yinghong Zhou¹, Jinying Lin², Jin Shao³, Qiliang Zuo², Shengfang Wang⁴, Annalena Wolff⁵, Dung Trung Nguyen⁶, Llew Rintoul⁷, Zhibin Du⁸, Yuantong Gu⁹, Yong Y Peng¹⁰, John A M Ramshaw¹¹, Xing Long¹², Yin Xiao¹³

Affiliations

¹ Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia; Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 51050, China; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: yinghongzhou@qut.edu.au.
² The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Implantology, Affiliated Stomatological Hospital of Xiamen Medical College, Fujian 361000, China; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia.
³ Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: jin.shao@connect.qut.edu.au.
⁴ Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: shengfang.wang@hdr.qut.edu.au.
⁵ Central Analytical Research Facility, Institute for Future Environments, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: annalena.wolff@qut.edu.au.
⁶ Department of Engineering and Computer Science, Seattle Pacific University, Seattle, WA 98119, USA. Electronic address: nguyend16@spu.edu.
⁷ Central Analytical Research Facility, Institute for Future Environments, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: l.rintoul@qut.edu.au.
⁸ Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: zhibin.du@qut.edu.au.
⁹ School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: yuantong.gu@qut.edu.au.
¹⁰ CSIRO Manufacturing, Bayview Avenue, Clayton, VIC 3168, Australia. Electronic address: yong.peng@csiro.au.
¹¹ CSIRO Manufacturing, Bayview Avenue, Clayton, VIC 3168, Australia.
¹² The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: longxing@whu.edu.cn.
¹³ The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia; Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 51050, China; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: yin.xiao@qut.edu.au.

PMID: 31260814
DOI: 10.1016/j.bone.2019.06.027

Abstract

Mineralization of bone is a dynamic process, involving a complex interplay between cells, secreted macromolecules, signaling pathways, and enzymatic reactions; the dysregulation of bone mineralization may lead to serious skeletal disorders, including hypophosphatemic rickets, osteoporosis, and rheumatoid arthritis. Very few studies have reported the role of osteocytes - the most abundant bone cells in the skeletal system and the major orchestrators of bone remodeling in bone mineralization, which is owed to their nature of being deeply embedded in the mineralized bone matrix. The Wnt/β-catenin signaling pathway is actively involved in various life processes including osteogenesis; however, the role of Wnt/β-catenin signaling in the terminal mineralization of bone, especially in the regulation of osteocytes, is largely unknown. This research demonstrates that during the terminal mineralization process, the Wnt/β-catenin pathway is downregulated, and when Wnt/β-catenin signaling is activated in osteocytes, dendrite development is suppressed and the expression of dentin matrix protein 1 (DMP1) is inhibited. Aberrant activation of Wnt/β-catenin signaling in osteocytes leads to the spontaneous deposition of extra-large mineralized nodules on the surface of collagen fibrils. The altered mineral crystal structure and decreased bonding force between minerals and the organic matrix indicate the inferior integration of minerals and collagen. In conclusion, Wnt/β-catenin signaling plays a critical role in the terminal differentiation of osteocytes and as such, targeting Wnt/β-catenin signaling in osteocytes may serve as a potential therapeutic approach for the management of bone-related diseases.

Keywords: Cell signaling; Dentin Matrix Protein 1 (DMP1); Mineralization; Osteocyte; Osteogenesis; Wnt/β-catenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers / metabolism
Calcification, Physiologic*
Cell Line
Crystallization
Mice, Inbred C57BL
Osteocytes / metabolism*
Osteocytes / ultrastructure
Swine
Wnt Signaling Pathway*

Substances

Biomarkers