Exploring the Cellular and Molecular Mechanism of Discoidin Domain Receptors (DDR1 and DDR2) in Bone Formation, Regeneration, and Its Associated Disease Conditions

Arokia Vijaya Anand Mariadoss; Chau-Zen Wang

doi:10.3390/ijms241914895

Exploring the Cellular and Molecular Mechanism of Discoidin Domain Receptors (DDR1 and DDR2) in Bone Formation, Regeneration, and Its Associated Disease Conditions

Int J Mol Sci. 2023 Oct 4;24(19):14895. doi: 10.3390/ijms241914895.

Authors

Arokia Vijaya Anand Mariadoss¹, Chau-Zen Wang^{1

2

3

4

5

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Affiliations

¹ Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
² Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
³ Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁴ Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁵ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
⁶ College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan.

Abstract

The tyrosine kinase family receptor of discoidin domain receptors (DDR1 and DDR2) is known to be activated by extracellular matrix collagen catalytic binding protein receptors. They play a remarkable role in cell proliferation, differentiation, migration, and cell survival. DDR1 of the DDR family regulates matrix-metalloproteinase, which causes extracellular matrix (ECM) remodeling and reconstruction during unbalanced homeostasis. Collagenous-rich DDR1 triggers the ECM of cartilage to regenerate the cartilage tissue in osteoarthritis (OA) and temporomandibular disorder (TMD). Moreover, DDR2 is prominently present in the fibroblasts, smooth muscle cells, myofibroblasts, and chondrocytes. It is crucial in generating and breaking collagen vital cellular activities like proliferation, differentiation, and adhesion mechanisms. However, the deficiency of DDR1 rather than DDR2 was detrimental in cases of OA and TMDs. DDR1 stimulated the ECM cartilage and improved bone regeneration. Based on the above information, we made an effort to outline the advancement of the utmost promising DDR1 and DDR2 regulation in bone and cartilage, also summarizing their structural, biological activity, and selectivity.

Keywords: DDR1; DDR2; bone regeneration; cartilage; osteoarthritis; tyrosine kinase.

Publication types

Review

MeSH terms

Collagen / metabolism
Discoidin Domain Receptor 1 / metabolism
Discoidin Domain Receptors
Osteogenesis*
Receptor Protein-Tyrosine Kinases / metabolism
Receptors, Mitogen* / genetics
Receptors, Mitogen* / metabolism

Substances

Discoidin Domain Receptors
Receptors, Mitogen
Receptor Protein-Tyrosine Kinases
Collagen
Discoidin Domain Receptor 1

Grants and funding

This study was supported by the Ministry of Science and Technology, Taiwan (NSTC 111-2320-B-037-008-MY2), Taiwan. The Orthopedic Research Center and Regeneration Medicine and Cell Therapy Research Center in Kaohsiung Medical University is acknowledged for its research resources and equipment. The funders had no conflicts of interest in the study design, the data collection and analysis, the decision to publish, or the manuscript preparation.