Progress of developmental mechanism of subtype H vessels in osteonecrosis of the femoral head_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

MA Jinhui ¹ , REN Yansong ² ,  WANG Bailiang ¹ ,  SUN Wei ¹ , YUE Debo ¹ , WANG Weiguo ¹

1. Department of Orthopedic Surgery, China-Japan Friendship Hospital, Beijing, 100029, P.R.China;
2. Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, P.R.China;

Corresponding author：

WANG Bailiang, Email: wang_orthopaedic@126.com; SUN Wei, Email: sun887@163.com

Keywords：

Subtype H vessels; osteonecrosis of the femoral head; angiogenesis; osteogenesis

DOI：

10.7507/1002-1892.202103159

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To review the research progress of subtype H vessels in the occurrence and development of osteonecrosis of the femoral head (ONFH).Methods The relevant domestic and foreign literature was extensively reviewed. The histological features, biological mechanism of subtype H vessels involved in promoting of osteogenesis, and the role and application of the subtype H vessels in ONFH were summarized.Results The subtype H vessel is a newly discovered bone vessel, mainly distributed in metaphysis and subperiosteum, highly expressing endomucin and CD31. The subtype H vessel has a dense arrangement of Runx2⁺ early osteoprogenitors, collagen type Ⅰα⁺ osteoblast cells, and Osterix⁺ osteoprogenitors that have the ability to induce osteogenesis and angiogenesis. Factors such as platelet-derived growth factor BB, slit guidance ligand 3, hypoxia inducible factor 1α, Notch signaling pathway, and vascular endothelial growth factor are involved in the mechanism of subtype H vessels in promoting osteogenesis.Conclusion Subtype H vessels play an important role in the regulation of angiogenesis and osteogenesis during bone tissue repair and reconstruction. The discovery of subtype H vessels provides new insights into the molecular and cellular mechanisms of osteogenesis and angiogenesis coupling. In the future, new techniques targeting the regulation of subtype H blood vessels may become a promising method for the treatment of ONFH.

Citation： MA Jinhui, REN Yansong, WANG Bailiang, SUN Wei, YUE Debo, WANG Weiguo. Progress of developmental mechanism of subtype H vessels in osteonecrosis of the femoral head. Chinese Journal of Reparative and Reconstructive Surgery, 2021, 35(11): 1486-1491. doi: 10.7507/1002-1892.202103159 Copy

1.	Mont MA, Salem HS, Piuzzi NS, et al. Nontraumatic osteonecrosis of the femoral head: where do we stand today?: A 5-year update. J Bone Joint Surg (Am), 2020, 102(12): 1084-1099.
2.	Tan B, Li W, Zeng P, et al. Epidemiological study based on China osteonecrosis of the femoral head database. Orthop Surg, 2021, 13(1): 153-160.
3.	Cohen-Rosenblum A, Cui Q. Osteonecrosis of the femoral head. Orthop Clin North Am, 2019, 50: 139-149.
4.	赵丁岩, 俞庆声, 郭万首, 等. 淫羊藿苷对激素诱导损伤人股骨头微血管内皮细胞蛋白质表达谱的影响. 中华医学杂志, 2016, 96(13): 1026-1030.
5.	路玉峰, 郭万首, 程立明. 骨微循环内皮细胞在激素性股骨头坏死发病机制的作用研究进展. 中国矫形外科杂志, 2015, 23(1): 47-51.
6.	Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature, 2014, 507(7492): 323-328.
7.	Ramasamy SK, Kusumbe AP, Wang L, et al. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature, 2014, 507(7492): 376-380.
8.	Wang L, Zhou F, Zhang P, et al. Human type H vessels are a sensitive biomarker of bone mass. Cell Death Dis, 2017, 8(5): e2760. doi: 10.1038/cddis.2017.36.
9.	卢键森, 柳鑫, 曾春, 等. H-型血管在骨关节炎软骨下骨中的表达及作用. 中国组织工程研究, 2017, 21(20): 3135-3140.
10.	Gao F, Mao T, Zhang Q, et al. H subtype vascular endothelial cells in human femoral head: an experimental verification. Ann Palliat Med, 2020, 9(4): 1497-1505.
11.	Schipani E, Maes C, Carmeliet G, et al. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J Bone Miner Res, 2009, 24(8): 1347-1353.
12.	Maes C. Role and regulation of vascularization processes in endochondral bones. Calcif Tissue Int, 2013, 92(4): 307-323.
13.	Xie H, Cui Z, Wang L, et al. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med, 2014, 20(11): 1270-1278.
14.	Xu R, Yallowitz A, Qin A, et al. Targeting skeletal endothelium to ameliorate bone loss. Nat Med, 2018, 24(6): 823-833.
15.	Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med, 2003, 9(6): 677-684.
16.	Jones DT, Harris AL. Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1 transactivation and DNA binding. Mol Cancer Ther, 2006, 5(9): 2193-2202.
17.	Ramasamy SK, Kusumbe AP, Schiller M, et al. Blood flow controls bone vascular function and osteogenesis. Nat Commun, 2016, 7: 13601. doi: 10.1038/ncomms13601.
18.	Ball SG, Shuttleworth CA, Kielty CM. Mesenchymal stem cells and neovascularization: role of platelet-derived growth factor receptors. J Cell Mol Med, 2007, 11(5): 1012-1030.
19.	Wang H, Yin Y, Li W, et al. Over-expression of PDGFR-β promotes PDGF-induced proliferation, migration, and angiogenesis of EPCs through PI3K/Akt signaling pathway. PLoS One, 2012, 7(2): e30503. doi: 10.1371/journal.pone.0030503.
20.	Fiedler J, Etzel N, Brenner RE. To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF. J Cell Biochem, 2004, 93(5): 990-998.
21.	Bronckaers A, Hilkens P, Martens W, et al. Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis. Pharmacol Ther, 2014, 143(2): 181-196.
22.	Nassiri SM, Rahbarghazi R. Interactions of mesenchymal stem cells with endothelial cells. Stem Cells Dev, 2014, 23(4): 319-332.
23.	Olsson AK, Dimberg A, Kreuger J, et al. VEGF receptor signalling-in control of vascular function. Nat Rev Mol Cell Biol, 2006, 7(5): 359-371.
24.	Caplan AI, Correa D. PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs. J Orthop Res, 2011, 29(12): 1795-1803.
25.	Long H, Sabatier C, Ma L, et al. Conserved roles for Slit and Robo proteins in midline commissural axon guidance. Neuron, 2004, 42(2): 213-223.
26.	Zhang B, Dietrich UM, Geng JG, et al. Repulsive axon guidance molecule Slit3 is a novel angiogenic factor. Blood, 2009, 114(19): 4300-4309.
27.	Geutskens SB, Andrews WD, van Stalborch AM, et al. Control of human hematopoietic stem/progenitor cell migration by the extracellular matrix protein Slit3. Lab Invest, 2012, 92(8): 1129-1139.
28.	Kim BJ, Lee YS, Lee SY, et al. Osteoclast-secreted SLIT3 coordinates bone resorption and formation. J Clin Invest, 2018, 128(4): 1429-1441.
29.	Kerachian MA, Harvey EJ, Cournoyer D, et al. Avascular necrosis of the femoral head: vascular hypotheses. Endothelium, 2006, 13(4): 237-244.
30.	Garcia P, Pieruschka A, Klein M, et al. Temporal and spatial vascularization patterns of unions and nonunions: role of vascular endothelial growth factor and bone morphogenetic proteins. J Bone Joint Surg (Am), 2012, 94(1): 49-58.
31.	Lane NE, Mohan G, Yao W, et al. Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity. Bone Rep, 2018, 9: 181-187.
32.	Chai Y, Su J, Hong W, et al. Antenatal corticosteroid therapy attenuates angiogenesis through inhibiting osteoclastogenesis in young mice. Front Cell Dev Biol, 2020, 8: 601188. doi: 10.3389/fcell.2020.601188.
33.	Peng Y, Lv S, Li Y, et al. Glucocorticoids disrupt skeletal angiogenesis through transrepression of NF-κB-mediated preosteoclast Pdgfb transcription in young mice. J Bone Miner Res, 2020, 35(6): 1188-1202.
34.	Johnson EO, Soultanis K, Soucacos PN. Vascular anatomy and microcirculation of skeletal zones vulnerable to osteonecrosis: vascularization of the femoral head. Orthop Clin North Am, 2004, 35(3): 285-291.
35.	Weinstein RS, Hogan EA, Borrelli MJ, et al. The pathophysiological sequence of glucocorticoid-induced osteonecrosis of the femoral head in male mice. Endocrinology, 2017, 158(11): 3817-3831.
36.	Forsythe JA, Jiang BH, Iyer NV, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol, 1996, 16(9): 4604-4613.
37.	Ding H, Gao YS, Hu C, et al. HIF-1α transgenic bone marrow cells can promote tissue repair in cases of corticosteroid-induced osteonecrosis of the femoral head in rabbits. PLoS One, 2013, 8(5): e63628. doi: 10.1371/journal.pone.0063628.
38.	Dai Y, Xu M, Wang Y, et al. HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia. J Mol Cell Cardiol, 2007, 42(6): 1036-1044.
39.	Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med, 2004, 10(8): 858-864.
40.	Kelly BD, Hackett SF, Hirota K, et al. Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ Res, 2003, 93(11): 1074-1081.
41.	Deckers MM, Karperien M, van der Bent C, et al. Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology, 2000, 141(5): 1667-1674.
42.	Mayr-Wohlfart U, Waltenberger J, Hausser H, et al. Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone, 2002, 30(3): 472-477.
43.	Mayer H, Bertram H, Lindenmaier W, et al. Vascular endothelial growth factor (VEGF-A) expression in human mesenchymal stem cells: autocrine and paracrine role on osteoblastic and endothelial differentiation. J Cell Biochem, 2005, 95(4): 827-839.
44.	Yang M, Li CJ, Xiao Y, et al. Ophiopogonin D promotes bone regeneration by stimulating CD31^hiEMCN^hi vessel formation. Cell Prolif, 2020, 53(3): e12784. doi: 10.1111/cpr.12784.
45.	Song C, Cao J, Lei Y, et al. Nuciferine prevents bone loss by disrupting multinucleated osteoclast formation and promoting type H vessel formation. FASEB J, 2020, 34(3): 4798-4811.
46.	Jing X, Du T, Yang X, et al. Desferoxamine protects against glucocorticoid-induced osteonecrosis of the femoral head via activating HIF-1α expression. J Cell Physiol, 2020, 235(12): 9864-9875.

1. Mont MA, Salem HS, Piuzzi NS, et al. Nontraumatic osteonecrosis of the femoral head: where do we stand today?: A 5-year update. J Bone Joint Surg (Am), 2020, 102(12): 1084-1099.
2. Tan B, Li W, Zeng P, et al. Epidemiological study based on China osteonecrosis of the femoral head database. Orthop Surg, 2021, 13(1): 153-160.
3. Cohen-Rosenblum A, Cui Q. Osteonecrosis of the femoral head. Orthop Clin North Am, 2019, 50: 139-149.
4. 赵丁岩, 俞庆声, 郭万首, 等. 淫羊藿苷对激素诱导损伤人股骨头微血管内皮细胞蛋白质表达谱的影响. 中华医学杂志, 2016, 96(13): 1026-1030.
5. 路玉峰, 郭万首, 程立明. 骨微循环内皮细胞在激素性股骨头坏死发病机制的作用研究进展. 中国矫形外科杂志, 2015, 23(1): 47-51.
6. Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature, 2014, 507(7492): 323-328.
7. Ramasamy SK, Kusumbe AP, Wang L, et al. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature, 2014, 507(7492): 376-380.
8. Wang L, Zhou F, Zhang P, et al. Human type H vessels are a sensitive biomarker of bone mass. Cell Death Dis, 2017, 8(5): e2760. doi: 10.1038/cddis.2017.36.
9. 卢键森, 柳鑫, 曾春, 等. H-型血管在骨关节炎软骨下骨中的表达及作用. 中国组织工程研究, 2017, 21(20): 3135-3140.
10. Gao F, Mao T, Zhang Q, et al. H subtype vascular endothelial cells in human femoral head: an experimental verification. Ann Palliat Med, 2020, 9(4): 1497-1505.
11. Schipani E, Maes C, Carmeliet G, et al. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J Bone Miner Res, 2009, 24(8): 1347-1353.
12. Maes C. Role and regulation of vascularization processes in endochondral bones. Calcif Tissue Int, 2013, 92(4): 307-323.
13. Xie H, Cui Z, Wang L, et al. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med, 2014, 20(11): 1270-1278.
14. Xu R, Yallowitz A, Qin A, et al. Targeting skeletal endothelium to ameliorate bone loss. Nat Med, 2018, 24(6): 823-833.
15. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med, 2003, 9(6): 677-684.
16. Jones DT, Harris AL. Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1 transactivation and DNA binding. Mol Cancer Ther, 2006, 5(9): 2193-2202.
17. Ramasamy SK, Kusumbe AP, Schiller M, et al. Blood flow controls bone vascular function and osteogenesis. Nat Commun, 2016, 7: 13601. doi: 10.1038/ncomms13601.
18. Ball SG, Shuttleworth CA, Kielty CM. Mesenchymal stem cells and neovascularization: role of platelet-derived growth factor receptors. J Cell Mol Med, 2007, 11(5): 1012-1030.
19. Wang H, Yin Y, Li W, et al. Over-expression of PDGFR-β promotes PDGF-induced proliferation, migration, and angiogenesis of EPCs through PI3K/Akt signaling pathway. PLoS One, 2012, 7(2): e30503. doi: 10.1371/journal.pone.0030503.
20. Fiedler J, Etzel N, Brenner RE. To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF. J Cell Biochem, 2004, 93(5): 990-998.
21. Bronckaers A, Hilkens P, Martens W, et al. Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis. Pharmacol Ther, 2014, 143(2): 181-196.
22. Nassiri SM, Rahbarghazi R. Interactions of mesenchymal stem cells with endothelial cells. Stem Cells Dev, 2014, 23(4): 319-332.
23. Olsson AK, Dimberg A, Kreuger J, et al. VEGF receptor signalling-in control of vascular function. Nat Rev Mol Cell Biol, 2006, 7(5): 359-371.
24. Caplan AI, Correa D. PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs. J Orthop Res, 2011, 29(12): 1795-1803.
25. Long H, Sabatier C, Ma L, et al. Conserved roles for Slit and Robo proteins in midline commissural axon guidance. Neuron, 2004, 42(2): 213-223.
26. Zhang B, Dietrich UM, Geng JG, et al. Repulsive axon guidance molecule Slit3 is a novel angiogenic factor. Blood, 2009, 114(19): 4300-4309.
27. Geutskens SB, Andrews WD, van Stalborch AM, et al. Control of human hematopoietic stem/progenitor cell migration by the extracellular matrix protein Slit3. Lab Invest, 2012, 92(8): 1129-1139.
28. Kim BJ, Lee YS, Lee SY, et al. Osteoclast-secreted SLIT3 coordinates bone resorption and formation. J Clin Invest, 2018, 128(4): 1429-1441.
29. Kerachian MA, Harvey EJ, Cournoyer D, et al. Avascular necrosis of the femoral head: vascular hypotheses. Endothelium, 2006, 13(4): 237-244.
30. Garcia P, Pieruschka A, Klein M, et al. Temporal and spatial vascularization patterns of unions and nonunions: role of vascular endothelial growth factor and bone morphogenetic proteins. J Bone Joint Surg (Am), 2012, 94(1): 49-58.
31. Lane NE, Mohan G, Yao W, et al. Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity. Bone Rep, 2018, 9: 181-187.
32. Chai Y, Su J, Hong W, et al. Antenatal corticosteroid therapy attenuates angiogenesis through inhibiting osteoclastogenesis in young mice. Front Cell Dev Biol, 2020, 8: 601188. doi: 10.3389/fcell.2020.601188.
33. Peng Y, Lv S, Li Y, et al. Glucocorticoids disrupt skeletal angiogenesis through transrepression of NF-κB-mediated preosteoclast Pdgfb transcription in young mice. J Bone Miner Res, 2020, 35(6): 1188-1202.
34. Johnson EO, Soultanis K, Soucacos PN. Vascular anatomy and microcirculation of skeletal zones vulnerable to osteonecrosis: vascularization of the femoral head. Orthop Clin North Am, 2004, 35(3): 285-291.
35. Weinstein RS, Hogan EA, Borrelli MJ, et al. The pathophysiological sequence of glucocorticoid-induced osteonecrosis of the femoral head in male mice. Endocrinology, 2017, 158(11): 3817-3831.
36. Forsythe JA, Jiang BH, Iyer NV, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol, 1996, 16(9): 4604-4613.
37. Ding H, Gao YS, Hu C, et al. HIF-1α transgenic bone marrow cells can promote tissue repair in cases of corticosteroid-induced osteonecrosis of the femoral head in rabbits. PLoS One, 2013, 8(5): e63628. doi: 10.1371/journal.pone.0063628.
38. Dai Y, Xu M, Wang Y, et al. HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia. J Mol Cell Cardiol, 2007, 42(6): 1036-1044.
39. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med, 2004, 10(8): 858-864.
40. Kelly BD, Hackett SF, Hirota K, et al. Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ Res, 2003, 93(11): 1074-1081.
41. Deckers MM, Karperien M, van der Bent C, et al. Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology, 2000, 141(5): 1667-1674.
42. Mayr-Wohlfart U, Waltenberger J, Hausser H, et al. Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone, 2002, 30(3): 472-477.
43. Mayer H, Bertram H, Lindenmaier W, et al. Vascular endothelial growth factor (VEGF-A) expression in human mesenchymal stem cells: autocrine and paracrine role on osteoblastic and endothelial differentiation. J Cell Biochem, 2005, 95(4): 827-839.
44. Yang M, Li CJ, Xiao Y, et al. Ophiopogonin D promotes bone regeneration by stimulating CD31^hiEMCN^hi vessel formation. Cell Prolif, 2020, 53(3): e12784. doi: 10.1111/cpr.12784.
45. Song C, Cao J, Lei Y, et al. Nuciferine prevents bone loss by disrupting multinucleated osteoclast formation and promoting type H vessel formation. FASEB J, 2020, 34(3): 4798-4811.
46. Jing X, Du T, Yang X, et al. Desferoxamine protects against glucocorticoid-induced osteonecrosis of the femoral head via activating HIF-1α expression. J Cell Physiol, 2020, 235(12): 9864-9875.

Chinese Journal of Reparative and Reconstructive Surgery

Progress of developmental mechanism of subtype H vessels in osteonecrosis of the femoral head

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content