Progress in the regulation of bone remodeling at the cellular level_Journal of Biomedical Engineering

Authors：

HU Yuanbo , WANG Lesha , JIANG Lei , XU Huazi ,  ZHU Sipin

The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R.China;

Corresponding author：

ZHU Sipin, Email: sipinzhu@163.com

Keywords：

bone remodeling; osteoclast; osteoblast; osteocyte

DOI：

10.7507/1001-5515.201606011

Video：

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Bone remodeling requires an intimate cross-talk between osteoclasts and osteoblasts and is tightly coordinated with regulatory proteins that interact through complex autocrine/paracrine processes. Osteocytes, bone lining cells, osteomacs and vascular endothelial cells also regulate bone remodeling in the basic multicellular unit (BMU) via cell signaling networks of ligand-receptor complexes. In addition, through secreted and membrane-bound factors in the bone microenvironment, T and B lymphocytes mediate bone homeostasis for osteoimmunology. Osteoporosis and other bone diseases occur because multicellular communication within the BMU is disrupted. This review focuses on the roles of the cells in the BMU and the interaction between these cells and the factors involved in regulating bone remodeling at the cellular level. Understanding the process of bone remodeling and related genes could help us to lay the foundation for drug development against bone diseases.

Citation： HU Yuanbo, WANG Lesha, JIANG Lei, XU Huazi, ZHU Sipin. Progress in the regulation of bone remodeling at the cellular level. Journal of Biomedical Engineering, 2017, 34(3): 471-479. doi: 10.7507/1001-5515.201606011 Copy

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2.	Niedźwiedzki T, Filipowska J. Bone remodeling in the context of cellular and systemic regulation: the role of osteocytes and the nervous system. J Mol Endocrinol, 2015, 55(2): R23-R36.
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14.	Koide N, Kondo Y, Odkhuu E, et al. Inhibition of receptor activator of nuclear factor-κB ligand-or lipopolysaccharide-induced osteoclast formation by conophylline through downregulation of CREB. Immunol Lett, 2014, 161(1): 31-37.
15.	Johnson R W, Mcgregor N E, Brennan H J, et al. Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone. Bone, 2015, 81: 343-351.
16.	Wozney J M, Rosen V, Celeste A J, et al. Novel regulators of bone formation: molecular clones and activities. Science, 1988, 242(4885): 1528-1534.
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18.	Tanaka K, Hashizume M, Mihara M, et al. Anti-interleukin-6 receptor antibody prevents systemic bone mass loss via reducing the number of osteoclast precursors in bone marrow in a collagen-induced arthritis model. Clin Exp Immunol, 2014, 175(2): 172-180.
19.	Lu Lei, Huang Jinghui, Zhang Xu, et al. Changes of temporomandibular joint and semaphorin 4D/Plexin-B1 expression in a mouse model of incisor malocclusion. Journal of oral & facial pain and headache, 2014, 28(1): 68-79.
20.	Sato K, Itoh T, Kato T, et al. Serum-free isolation and culture system to enhance the proliferation and bone regeneration of adipose tissue-derived mesenchymal stem cells. In Vitro Cell Dev Biol Anim, 2015, 51(5): 515-529.
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26.	Hu Minyi, Tian G W, Gibbons D E, et al. Dynamic fluid flow induced mechanobiological modulation of in situ osteocyte Calcium oscillations. Arch Biochem Biophys, 2015, 579: 55-61.
27.	Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int, 2014, 94(1): 25-34.
28.	Horwood N J. Macrophage polarization and bone formation: a review. Clin Rev Allergy Immunol, 2016, 51(1): 79-86.
29.	Brandi M L, Collin-Osdoby P. Vascular biology and the skeleton. J Bone Miner Res, 2006, 21(2): 183-192.
30.	Tomlinson R E, Silva M J. HIF-1α regulates bone formation after osteogenic mechanical loading. Bone, 2015, 73: 98-104.
31.	Meednu N, Zhang Hengwei, Owen T, et al. Production of RANKL by memory B cells: a Link between B cells and bone erosion in rheumatoid arthritis. Arthritis & rheumatology (Hoboken, N. J.), 2016, 68(4): 805-816.
32.	Hu Y, Ek-Rylander B, Wendel M, et al. Reciprocal effects of Interferon-γ and IL-4 on differentiation to osteoclast-like cells by RANKL or LPS. Oral Dis, 2014, 20(7): 682-692.

1. Boyle W J, Simonet W S, Lacey D L. Osteoclast differentiation and activation. Nature, 2003, 423(6937): 337-342.
2. Niedźwiedzki T, Filipowska J. Bone remodeling in the context of cellular and systemic regulation: the role of osteocytes and the nervous system. J Mol Endocrinol, 2015, 55(2): R23-R36.
3. Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST) Hum Mol Genet, 2001, 10(5): 537-543.
4. Brunkow M E, Gardner J C, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet, 2001, 68(3): 577-589.
5. Kim H J, Yoon H J, Yoon K A, et al. Lipocalin-2 inhibits osteoclast formation by suppressing the proliferation and differentiation of osteoclast lineage cells. Exp Cell Res, 2015, 334(2): 301-309.
6. Zhao Chen, Irie N, Takada Yasunari, et al. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab, 2006, 4(2): 111-121.
7. Delaisse J M. The reversal phase of the bone-remodeling cycle: cellular prerequisites for coupling resorption and formation. Bonekey Rep, 2014, 3(3): 561.
8. Väänänen H K, Horton M. The osteoclast clear zone is a specialized cell-extracellular matrix adhesion structure. J Cell Sci, 1995, 108(Pt 8): 2729-2732.
9. Kleinhans C, Schmid F F, Schmid F V, et al. Comparison of osteoclastogenesis and resorption activity of human osteoclasts on tissue culture polystyrene and on natural extracellular bone matrix in 2D and 3D. J Biotechnol, 2015, 205: 101-110.
10. Honma M, Ikebuchi Y, Kariya Y, et al. Regulatory mechanisms of RANKL presentation to osteoclast precursors. Curr Osteoporos Rep, 2014, 12(1): 115-120.
11. Martin T J, Sims N A. RANKL/OPG; critical role in bone physiology. Rev Endocr Metab Disord, 2015, 16(2): 131-139.
12. Sapir-Koren R, Livshits G. Osteocyte control of bone remodeling: is sclerostin a key molecular coordinator of the balanced bone resorption-formation cycles?. Osteoporos Int, 2014, 25(12): 2685-2700.
13. Yuan X, Cao J, Liu T, et al. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss. Cell Death Differ, 2015, 22(12): 2046-2057.
14. Koide N, Kondo Y, Odkhuu E, et al. Inhibition of receptor activator of nuclear factor-κB ligand-or lipopolysaccharide-induced osteoclast formation by conophylline through downregulation of CREB. Immunol Lett, 2014, 161(1): 31-37.
15. Johnson R W, Mcgregor N E, Brennan H J, et al. Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone. Bone, 2015, 81: 343-351.
16. Wozney J M, Rosen V, Celeste A J, et al. Novel regulators of bone formation: molecular clones and activities. Science, 1988, 242(4885): 1528-1534.
17. Thudium C S, Moscatelli I, Flores C, et al. A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation. Calcif Tissue Int, 2014, 95(1): 83-93.
18. Tanaka K, Hashizume M, Mihara M, et al. Anti-interleukin-6 receptor antibody prevents systemic bone mass loss via reducing the number of osteoclast precursors in bone marrow in a collagen-induced arthritis model. Clin Exp Immunol, 2014, 175(2): 172-180.
19. Lu Lei, Huang Jinghui, Zhang Xu, et al. Changes of temporomandibular joint and semaphorin 4D/Plexin-B1 expression in a mouse model of incisor malocclusion. Journal of oral & facial pain and headache, 2014, 28(1): 68-79.
20. Sato K, Itoh T, Kato T, et al. Serum-free isolation and culture system to enhance the proliferation and bone regeneration of adipose tissue-derived mesenchymal stem cells. In Vitro Cell Dev Biol Anim, 2015, 51(5): 515-529.
21. Ellies D L, Economou A, Viviano B, et al. Wise regulates bone deposition through genetic interactions with Lrp5. PLoS One, 2014, 9(5): e96257.
22. Beederman M, Lamplot J D, Nan G, et al. BMP signaling in mesenchymal stem cell differentiation and bone formation. J Biomed Sci Eng, 2013, 6(8A): 32-52.
23. Anderson H C. Matrix vesicles and calcification. Curr Rheumatol Rep, 2003, 5(3): 222-226.
24. Park K, Ju W C, Yeo J H, et al. Increased OPG/RANKL ratio in the conditioned medium of soybean-treated osteoblasts suppresses RANKL-induced osteoclast differentiation. Int J Mol Med, 2014, 33(1): 178-184.
25. Chukkapalli S, Levi E, Rishi A K, et al. PTHrP attenuates osteoblast cell death and apoptosis induced by a novel class of anti-cancer agents. Endocrine, 2016, 51(3): 534-544.
26. Hu Minyi, Tian G W, Gibbons D E, et al. Dynamic fluid flow induced mechanobiological modulation of in situ osteocyte Calcium oscillations. Arch Biochem Biophys, 2015, 579: 55-61.
27. Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int, 2014, 94(1): 25-34.
28. Horwood N J. Macrophage polarization and bone formation: a review. Clin Rev Allergy Immunol, 2016, 51(1): 79-86.
29. Brandi M L, Collin-Osdoby P. Vascular biology and the skeleton. J Bone Miner Res, 2006, 21(2): 183-192.
30. Tomlinson R E, Silva M J. HIF-1α regulates bone formation after osteogenic mechanical loading. Bone, 2015, 73: 98-104.
31. Meednu N, Zhang Hengwei, Owen T, et al. Production of RANKL by memory B cells: a Link between B cells and bone erosion in rheumatoid arthritis. Arthritis & rheumatology (Hoboken, N. J.), 2016, 68(4): 805-816.
32. Hu Y, Ek-Rylander B, Wendel M, et al. Reciprocal effects of Interferon-γ and IL-4 on differentiation to osteoclast-like cells by RANKL or LPS. Oral Dis, 2014, 20(7): 682-692.

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Progress in the regulation of bone remodeling at the cellular level

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