We also summarize the application of bone ECM in bone repair and regeneration. (2015). Osteopenia and decreased bone formation in osteonectin-deficient mice. Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization. Rep-Uk 6, 38814. doi: 10.1038/srep38814, Chen, X. D., Shi, S., Xu, T., Robey, P. G., Young, M. F. (2002). Deciphering the Relevance of Bone ECM Signaling. Mat. Tissue Eng. Therefore, collagen acts as a tissue scaffold, providing a matrix for anchoring cells and regulating the growth and osteogenic properties of osteoblasts. A PLGA/PLA scaffold was coated with dECM form human lung fibroblasts (hFDM) in bone defect repair by delivering BMP-2. Similar to nanofibrous HA scaffold, Shamaz et al. Chamieh et al. These are considered to be important for MSC homing and fate determination, such as adhesion, expansion, and spreading, through integrin receptors. Int. Moreover, periostin participates in collagen folding and fibrillogenesis, which is essential for matrix assembly and further maintains bone strength (Wen et al., 2018). D'Angelo E, Lindoso RS, Sensi F, Pucciarelli S, Bussolati B, Agostini M, Collino F. Front Oncol. However, due to the complexity and dynamics of its components, there has been no systematic analysis of the components of the ECM secreted by cells or tissues, and it is not clear if decellularized ECM can completely match the biochemical imprint of the native bone ECM. The extracellular matrix is comprised of non-cellular components within tissues that form an essential scaffold for cellular constituents. suspension of macromolecules that supports everything from local tissue growth to the maintenance of an entire organ In bone repair applications, cell-derived dECM combined with inorganic material to composite hybrid scaffolds, providing stronger osteoinductive properties and mechanical support. MEPE expression in osteocytes during orthodontic tooth movement. R-spondin-2 is a Wnt agonist that regulates osteoblast activity and bone mass. 7, 12. doi: 10.1038/s41413-019-0051-1, Elango, J., Robinson, J., Zhang, J., Bao, B., Ma, N., de Val, J., et al. It can promote osteoblast differentiation and enhance early bone mineralization to produce new bone in vivo. The levels of DMP1 and Sclerostin are greatly increased on collagen-based substrates with low stiffness, indicating enhanced osteocyte differentiation compared to ECM substrates with high stiffness (Mullen et al., 2013). 148, 203–303. Therefore, decellularized ECM scaffold obtained either from tissue in vivo or cultured cells in vitro is a promising strategy to induce bone regeneration and has a good clinical performance. doi: 10.1038/nrc2345, Belotti, D., Capelli, C., Resovi, A., Introna, M., Taraboletti, G. (2016). doi: 10.1101/cshperspect.a005058. Mol. The structure of the extracellular matrix differs in composition between tissue types but is essentially made up of collagen fibers, proteoglycans and multiadhesive matrix proteins that are secreted by cells. Sci. Biosci. Chem. doi: 10.1016/j.biomaterials.2014.10.012, Polo-Corrales, L., Latorre-Esteves, M., Ramirez-Vick, J. E. (2014). ECM-based scaffolds for bone tissue engineering can be divided into two types, that is, ECM-modified biomaterial scaffold and decellularized ECM scaffold. The multiple facets of periostin in bone metabolism. On the other hand, OCN promotes the differentiation of MSCs into osteoblasts, with the increase of extracellular calcium levels, ALP activity, and the mRNA expression of OPN and OCN (Carvalho et al., 2019a). doi: 10.1007/s12079-009-0076-0, Delany, A. M., Amling, M., Priemel, M., Howe, C., Baron, R., Canalis, E. (2000). doi: 10.2147/IJN.S124671, Onishi, T., Shimizu, T., Akahane, M., Omokawa, S., Okuda, A., Kira, T., et al. doi: 10.1016/j.jmbbm.2013.06.013, Noori, A., Ashrafi, S. J., Vaez-Ghaemi, R., Hatamian-Zaremi, A., Webster, T. J. KEYWORDS bioink, bone, cartilage, decellularization, extracellular matrix… Periostin action in bone. Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration. Matrix Gla protein inhibition of tooth mineralization. Obviously, the surface morphology and overall topology of ECM in scaffolds are significantly involved in determining their capacity for cell loading and growth in bone tissue engineering. doi: 10.1016/j.bone.2018.09.006, Bose, S., Roy, M., Bandyopadhyay, A. Circulating OCN not only acts as a hormone that regulates glucose and energy metabolism, but its concentration in serum can be used as a biochemical indicator of bone formation (Mizokami et al., 2017). doi: 10.1007/s00264-011-1391-7, Holm, E., Aubin, J. E., Hunter, G. K., Beier, F., Goldberg, H. A. (2015). Other ECM molecules, such as OPN, OCN, and DMP1, can regulate the proliferation of MSCs and osteogenesis. (2013). Pharmacol. Front. Because the grafts contain the native bone matrix, osteoblasts, and growth factors, they intrinsically possess osteoinductivity and osteoconductivity (Garcia-Gareta et al., 2015). J. Cell-derived dECM, rich in collagen, matrix macromolecules, and growth factors, has good biocompatibility and biodegradability, making it beneficial for the proliferation and osteogenic differentiation of MSCs, and can be used as cell culture matrix for bone regeneration medicine. demonstrated that a combination of decellularized adipose tissue (DAT) with adipose-derived stromal/stem cells (ASCs) is effective in the regenerative bone repair of mice critical-size femur defects. Integrative Analysis of Periostin in Primary and Advanced Prostate Cancer. doi: 10.3892/mmr.2018.8940, Wu, Y. (2016). This means that in addition to the different components of modified ECM to affect the cell behaviors in bone regeneration, different ECM contents also play different roles. doi: 10.2217/rme-2016-0042, Mizokami, A., Kawakubo-Yasukochi, T., Hirata, M. (2017). The authors declare no conflict of interest. OPN and BSP can act as a network to coordinate the function of osteoclasts. A dECM produced from non-bone tissue can also be used in bone regeneration. (2016). Matrix Biol. doi: 10.1042/BJ20090542, Kattimani, V., Lingamaneni, K. P., Yalamanchili, S., Mupparapu, M. (2019). Mater. Front. J. Mol. Regenerating bone with bioactive glass scaffolds: A review of in vivo studies in bone defect models. 23, 1199–1212. A dECM derived from the porous growth plate (GP) was fabricated to repair critical-sized rat cranial defects. Cell Biol. 2016, 6397820. doi: 10.1155/2016/6397820, Hu, W. S. (1992). It is composed predominantly of collagens, non-collagenous glycoproteins, hyaluronan and proteoglycans. Periosteum Extracellular-Matrix-Mediated Acellular Mineralization during Bone Formation. In addition, osteoclast surfaces and the number of osteoclasts are decreased in BSP knockout mice. doi: 10.1074/jbc.M500573200, Bonnans, C., Chou, J., Werb, Z. doi: 10.1159/000495482, Zhang, S. F., Wan, H. X., Wang, P., Liu, M. M., Li, G. C., Zhang, C. X., et al. PloS One 10, e0131105. J. doi: 10.1007/s00223-015-9996-2, Gluhak-Heinrich, J., Ye, L., Bonewald, L. F., Feng, J. Q., MacDougall, M., Harris, S. E., et al. doi: 10.2174/138161209787846739. Of glycoprotein in the bone matrix, osteonectin, also known as secreted protein acidic and rich in cysteine (SPARC), is a common representative. ECM scaffolds have unique advantages in all these areas. The ECM acts as a physical scaffold and substrate for cell adhesion, delivering biochemical and biomechanical signals for cells to initiate migration, differentiation, morphogenesis, and homeostasis (Yi et al., 2017). Extracellular matrix components One of the most abundant components of the bone marrow space, besides cells, is a variety of extracellular matrix components. Bone contains 100s of extracellular matrix (ECM) proteins and the ECM of the various bone tissue compartments plays essential roles directing the remodeling of bone through the coupled … Bone biomaterials and interactions with stem cells. Connect Tissue Res. Cell Endocrinol. Sclerostin is an important inhibitor of WNT/β-catenin signaling and regulates osteoblast matrix generation. In addition, 3D ECM scaffold produced from decellularized periosteum promoted bone mineralization by controlling the size and direction of mineral crystals in rabbit bone defect regeneration, suggesting the crucial role of periosteum ECM in efficient healing of fractures and bone regeneration (Lin et al., 2018). The decellularized ECM provides mechanical support for the regenerating cells and affects both their migration and cell fate decision (Gallie et al., 1989). 494, 110494. doi: 10.1016/j.mce.2019.110494, Liu, H. H., Peng, H. J., Wu, Y., Zhang, C., Cai, Y. doi: 10.1016/j.msec.2016.11.070, Clough, B. H., McCarley, M. R., Krause, U., Zeitouni, S., Froese, J. J., McNeill, E. P., et al. The implantation of osteogenic ECM sheets (OECMS) that retain the native collagen I and growth factors, together with HA, enhanced bone regeneration in a rat model of femoral non-union at 5 and 8 weeks. The OECMS contained TGF-β and BMP2, leading to increased osteoinduction and osteoconduction (Onishi et al., 2018). The bone marrow is located in the diaphysis, or shaft of long bones. The extracellular matrix at a glance. In this review, we briefly introduce the inorganic and organic ECM of bone tissue (Table 1), including collagenous and non-collagenous proteins, and summarize the effects of the ECM on osteoblast-lineage cells, including MSCs, osteoblasts, and osteocytes, and osteoclasts. Tissue Int. (Elite Ed) 9, 192–203. Res. , Coathup, M., Bandyopadhyay, a, affects DMP1 expression nitric oxide signaling in.. Kozloff K., Ou, G. Q., Weaver, V. M. ( 2019 ) matrix ( )! And activity of TGF-β as well as induce osteogenic differentiation of monocyte/macrophage precursors, involve bone! 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