Abstract

Bone regeneration repairs bone tissue lost due to trauma, fractures, and tumors, or absent due to congenital disorders. The extracellular matrix (ECM) is an intricate dynamic bio-environment with precisely regulated mechanical and biochemical properties. In bone, ECMs are involved in regulating cell adhesion, proliferation, and responses to growth factors, differentiation, and ultimately, the functional characteristics of the mature bone. Bone ECM can induce the production of new bone by osteoblast-lineage cells, such as MSCs, osteoblasts, and osteocytes and the absorption of bone by osteoclasts. With the rapid development of bone regenerative medicine, the osteoinductive, osteoconductive, and osteogenic potential of ECM-based scaffolds has attracted increasing attention. ECM-based scaffolds for bone tissue engineering can be divided into two types, that is, ECM-modified biomaterial scaffold and decellularized ECM scaffold. Tissue engineering strategies that utilize the functional ECM are superior at guiding the formation of specific tissues at the implantation site. In this review, we provide an overview of the function of various types of bone ECMs in bone tissue and their regulation roles in the behaviors of osteoblast-lineage cells and osteoclasts. We also summarize the application of bone ECM in bone repair and regeneration. A better understanding of the role of bone ECM in guiding cellular behavior and tissue function is essential for its future applications in bone repair and regenerative medicine.

Highlights

  • Trauma, fractures, congenital disease, or tumors can cause bone defects that are challenging to heal

  • Small Integrin-Binding Ligand N-Linked Glycoproteins/ SIBLINGs SIBLINGs are a family of glycophosphoproteins that includes bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein-1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE)

  • The osteogenic differentiation of mesenchymal stem cells (MSCs) can be divided into four steps: (i) the commitment step produces lineage-specific progenitor cells; (ii) the proliferative phase of osteoprogenitors, in which genes associated with the cell cycle and histone signals are expressed; (iii) the phase of extracellular matrix (ECM) secretion and morphological changes of immature osteoblasts; (iv) osteoid mineralization initiated by mature osteoblasts, which become terminally differentiated osteocytes (Paiva and Granjeiro, 2017)

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Summary

The Bone Extracellular Matrix in Bone Formation and Regeneration

Laboratory for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Laboratory for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China. ECMs are involved in regulating cell adhesion, proliferation, and responses to growth factors, differentiation, and the functional characteristics of the mature bone. With the rapid development of bone regenerative medicine, the osteoinductive, osteoconductive, and osteogenic potential of ECM-based scaffolds has attracted increasing attention. Tissue engineering strategies that utilize the functional ECM are superior at guiding the formation of specific tissues at the implantation site. We provide an overview of the function of various types of bone ECMs in bone tissue and their regulation roles in the behaviors of osteoblast-lineage cells and osteoclasts. We summarize the application of bone ECM in bone repair and regeneration. A better understanding of the role of bone ECM in guiding cellular behavior and tissue function is essential for its future applications in bone repair and regenerative medicine

INTRODUCTION
Organic ECM
Function in bone tissue
Inorganic ECM
Regulation of BMSCs by the ECM
Regulation of Osteoblasts by the ECM
Bone ECM Functions in MSCs
Biglycan Decorin DKO mice MSCs
Regulation of Osteocytes by the ECM
Type I collagen Type III collagen Osteonectin
Denatured forms of collagen
FUNCTION OF THE BONE ECM IN OSTEOCLASTS
External mechanical force
APPLICATION OF THE ECM FOR BONE TISSUE ENGINEERING
Biglycan Fibromodulin DKO mice Primary BMMs
Decellularized ECM Scaffold
Findings
CONCLUSIONS AND PROSPECTS
Full Text
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