Proteoglycans are essential components of the extracellular matrix with roles in bone development including endochondral ossification, collagen fibrillogenesis, and mineral deposition. They may enhance or inhibit cell signaling pathways, thus providing a method of intricate control over bone formation and resorption. The development of embryonic bone is nature’s blueprint for bone design. Understanding the role of proteoglycans in bone formation, as key bone-building materials, is essential for drafting a better blueprint for bone repair. (Kim and Lee, 2023) Molecular Matrix, Inc. designed Osteo-P® BGS, a hyper-crosslinked polysaccharide bone graft substitute, to model the intricate processes of embryonic bone development. Specifically, Osteo-P® BGS mimics proteoglycans and is osteoconductive for bone repair. To learn more about embryonic bone and proteoglycans see below or visit https://www.molecularmatrix.com/
7 Roles of Proteoglycans in Bone Formation
1. Osteoid – this is the unmineralized organic matrix secreted by osteoblasts in the early stages of bone formation. The osteoid is rich in proteoglycans which play a role in initial matrix organization and subsequent mineralization. (Pacifici et al., 2005)
2. Endochondral ossification – the process of bone formation where mesenchymal precursors differentiate into chondrocytes which are eventually replaced by bone tissue. Proteoglycans are present in the cartilage matrix where they help maintain structure and function until replaced by bone. (Poole et al., 1982; Settembre et al., 2008; Hayes et al., 2018)
3. Epiphyseal plate – the region of growing tissue near the ends of long bones in children and adolescents. Proteoglycans are abundant in the cartilage of the growth plate where they contribute to regulation of chondrocyte proliferation and differentiation. (Pacific et al., 2005; Melrose et al., 2016)
4. Bone matrix – proteoglycans like decorin, biglycan, and perlecan are involved in the regulation of mineral deposition and the organization of collagen fibers. They influence the mechanical properties of the bone and the ability to resist compressive forces. (Fisher et al., 1983; Lin 2020; Hayes et al., 2022)
5. Periosteum – the dense layer of vascular connective tissue enveloping the bones, except at the surfaces of the joints. The periosteum contains proteoglycans which are involved in bone appositional growth and repair. (Zhang et al., 2022)
6. Articular cartilage – the cartilage covering the ends of the bones at the joint. The articular cartilage is rich in proteoglycans which contribute to load-bearing and mechanical properties. (Hayes et al., 2018; Han et al., 2019)
7. Bone marrow – proteoglycans regulate the bone marrow microenvironment and have a role in hematopoiesis. (Papy-Garcia and Albanese, 2017)
References
Fisher LW, Termine JD, Dejter SW, Whitson SW, Yanagishita M, Kimura JH, et al. Proteoglycans of developing bone. The Journal of Biological Chemistry. 1983;258(10):6588-6594
Han B, Li Q, Wang C, Patel P, Adams SM, Doyran B, et al. Decorin regulates the Aggrecan network integrity and biomechanical functions of cartilage extracellular matrix. ACS Nano. 2019;13(10):11320-11333
Hayes AJ, Smith SM, Caterson B, Melrose J. Concise Review: Stem/Progenitor Cell Proteoglycans Decorated with 7-D-4, 4-C-3, and 3-B-3(-) Chondroitin Sulfate Motifs Are Morphogenetic Markers of Tissue Development. Stem Cells. 2018 Oct;36(10):1475-1486. doi: 10.1002/stem.2860. Epub 2018 Jul 31. PMID: 29893019; PMCID: PMC6381390.
Hayes AJ, Farrugia BL, Biose IJ, Bix GJ, Melrose J. Perlecan, a multi-functional, cell-instructive, matrix-stabilizing proteoglycan with roles in tissue development has relevance to connective tissue repair and regeneration. Frontiers in Cell and Development Biology. 2022;10:856261
Kim KD, Lee CC. “Osteogenic Cells and Microenvironment of Early Bone Development and Clinical Implication.” Frontiers in Spinal Neurosurgery, Ch. 7, edited by Wang, J.J., Wang G., Lv X., Sun Z., and Mahapure K.S., IntechOpen, 14 July 2023. DOI: 10.5772/intechopen.1002037
Lin X, Patil S, Gao YG, Qian A. The bone extracellular matrix in bone formation and regeneration. Frontiers in Pharmacology. 2020;11:757
Melrose J, Shu C, Whitelock JM, Lord MS. The cartilage extracellular matrix as a transient developmental scaffold for growth plate maturation. Matrix Biol. 2016 May-Jul;52-54:363-383. doi: 10.1016/j.matbio.2016.01.008. Epub 2016 Jan 23. PMID: 26807757.
Pacifici M, Shimo T, Gentili C. et al. Syndecan-3: a cell-surface heparan sulfate proteoglycan important for chondrocyte proliferation and function during limb skeletogenesis. J Bone Miner Metab 23, 191–199 (2005). https://doi.org/10.1007/s00774-004-0584-1
Papy-Garcia D, Albanese, P. Heparan sulfate proteoglycans as key regulators of the mesenchymal niche of hematopoietic stem cells. Glycoconj J 34, 377–391 (2017). https://doi.org/10.1007/s10719-017-9773-8
Poole AR, Pidoux I, Rosenberg L. Role of proteoglycans in endochondral ossification: Immunofluorescent localization of link protein and proteoglycan monomer in bovine fetal epiphyseal growth plate. The Journal of Cell Biology. 1982;92(2):249-260
Settembre C, Arteaga-Solis E, McKee MD, de Pablo R, Al Awqati Q, Ballabio A, et al. Proteoglycan desulfation determines the efficiency of chondrocyte autophagy and the extent of FGF signaling during endochondral ossification. Genes & Development. 2008;22(19):2645-2650
Zhang W, Wang N, Yang M, Sun T, Zhang J, Zhao Y, Huo N, Li Z. Periosteum and development of the tissue-engineered periosteum for guided bone regeneration. J Orthop Translat. 2022 Feb 16;33:41-54. doi: 10.1016/j.jot.2022.01.002. PMID: 35228996; PMCID: PMC8858911.
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