Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

WANG Yushun ^1,2 , ZHENG Jianrui ¹ , LUO Yuhong ¹ , CHEN Lei ¹ , PENG Zhigang ¹ , YE Gensen ¹ ,  WANG Deli ¹ ,  TAN Zhen ¹

1. Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Guangdong, 518000, P. R. China;
2. Shenzhen University Health Science Center, Shenzhen Guangdong, 518000, P. R. China;

Corresponding author：

WANG Deli, Email: wangdeliortho@outlook.com; TAN Zhen, Email: tanzeric@bjmu.edu.cn

Keywords：

Osteonecrosis of the femoral head; macrophage; osteoimmunology; chronic inflammation

DOI：

10.7507/1002-1892.202308026

Video：

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Objective To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. Methods Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. Results Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. Conclusion At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.

Citation： WANG Yushun, ZHENG Jianrui, LUO Yuhong, CHEN Lei, PENG Zhigang, YE Gensen, WANG Deli, TAN Zhen. Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head. Chinese Journal of Reparative and Reconstructive Surgery, 2024, 38(1): 119-124. doi: 10.7507/1002-1892.202308026 Copy

1.	Meng K, Liu Y, Ruan L, et al. Suppression of apoptosis in osteocytes, the potential way of natural medicine in the treatment of osteonecrosis of the femoral head. Biomed Pharmacother, 2023, 162: 114403.
2.	Zheng J, Yao Z, Xue L, et al. The role of immune cells in modulating chronic inflammation and osteonecrosis. Front Immunol, 2022, 13: 1064245.
3.	Quan H, Ren C, He Y, et al. Application of biomaterials in treating early osteonecrosis of the femoral head: Research progress and future perspectives. Acta biomaterialia, 2023, 164: 15-73.
4.	Lou P, Zhou G, Wei B, et al. Sclerotic zone in femoral head necrosis: from pathophysiology to therapeutic implications. EFORT Open Reviews, 2023, 8(6): 451-458.
5.	Wang J, Xu P, Zhou L. Comparison of current treatment strategy for osteonecrosis of the femoral head from the perspective of cell therapy. Front Cell Dev Biol, 2023, 11: 995816.
6.	Che Z, Song Y, Zhu L, et al. Emerging roles of growth factors in osteonecrosis of the femoral head. Front Genet, 2022, 13: 1037190.
7.	Wang X, Chen X, Lu L, et al. Alcoholism and osteoimmunology. Curr Med Chem, 2021, 28(9): 1815-1828.
8.	Tsukasaki M, Takayanagi H. Osteoimmunology: evolving concepts in bone-immune interactions in health and disease. Nat Rev Immunol, 2019, 19(10): 626-642.
9.	Saxena Y, Routh S, Mukhopadhaya A. Immunoporosis: role of innate immune cells in osteoporosis. Front Immunol, 2021, 12: 687037.
10.	Yang N, Liu Y. The role of the immune microenvironment in bone regeneration. Int J Med Sci, 2021, 18(16): 3697-3707.
11.	Vicaş RM, Bodog FD, Fugaru FO, et al. Histopathological and immunohistochemical aspects of bone tissue in aseptic necrosis of the femoral head. Rom J Morphol Embryol, 2020, 61(4): 1249-1258.
12.	Liang XZ, Liu XC, Li S, et al. IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head. J Orthop Surg Res, 2023, 18(1): 27.
13.	Wang B, Gong S, Shao W, et al. Comprehensive analysis of pivotal biomarkers, immune cell infiltration and therapeutic drugs for steroid-induced osteonecrosis of the femoral head. Bioengineered, 2021, 12(1): 5971-5984.
14.	Yu R, Zhang J, Zhuo Y, et al. ARG2, MAP4K5 and TSTA3 as diagnostic markers of steroid-induced osteonecrosis of the femoral head and their correlation with immune infiltration. Front Genet, 2021, 12: 691465.
15.	Zhao J, Zhang X, Guan J, et al. Identification of key biomarkers in steroid-induced osteonecrosis of the femoral head and their correlation with immune infiltration by bioinformatics analysis. BMC Musculoskelet Disord, 2022, 23(1): 67.
16.	Schlundt C, Fischer H, Bucher CH, et al. The multifaceted roles of macrophages in bone regeneration: A story of polarization, activation and time. Acta biomaterialia, 2021, 133: 46-57.
17.	Yao Y, Cai X, Ren F, et al. The macrophage-osteoclast axis in osteoimmunity and osteo-related diseases. Front Immunol, 2021, 12: 664871.
18.	Zhang Q, Sun W, Li T, et al. Polarization behavior of bone macrophage as well as associated osteoimmunity in glucocorticoid-induced osteonecrosis of the femoral head. J Inflamm Res, 2023, 16: 879-894.
19.	Viola A, Munari F, Sánchez-Rodríguez R, et al. The metabolic signature of macrophage responses. Front Immunol, 2019, 10: 1462.
20.	Wang C, Ma C, Gong L, et al. Macrophage polarization and its role in liver disease. Front Immunol, 2021, 12: 803037.
21.	Davis FM, Gallagher KA. Epigenetic mechanisms in monocytes/macrophages regulate inflammation in cardiometabolic and vascular disease. Arterioscler Thromb Vasc Biol, 2019, 39(4): 623-634.
22.	Orecchioni M, Ghosheh Y, Pramod AB, et al. Macrophage polarization: Different gene signatures in M1(LPS+) vs classically and M2(LPS-) vs alternatively activated macrophages. Front Immunol, 2019, 10: 1084.
23.	Tang PM, Nikolic-Paterson DJ, Lan HY. Macrophages: versatile players in renal inflammation and fibrosis. Nat Rev Nephrol, 2019, 15(3): 144-158.
24.	Gharavi AT, Hanjani NA, Movahed E, et al. The role of macrophage subtypes and exosomes in immunomodulation. Cell Mol Biol Lett, 2022, 27(1): 83.
25.	Williams DW, Vuong HE, Kim S, et al. Indigenous microbiota protects against inflammation-induced osteonecrosis. J Dent Res, 2020, 99(6): 676-684.
26.	Goodman SB, Maruyama M. Inflammation, bone healing and osteonecrosis: from bedside to bench. J Inflamm Res, 2020, 13: 913-923.
27.	Loi F, Córdova LA, Pajarinen J, et al. Inflammation, fracture and bone repair. Bone, 2016, 86: 119-130.
28.	ElHawary H, Baradaran A, Abi-Rafeh J, et al. Bone healing and inflammation: principles of fracture and repair. Semin Plast Surg, 2021, 35(3): 198-203.
29.	Maruyama M, Rhee C, Utsunomiya T, et al. Modulation of the inflammatory response and bone healing. Front Endocrinol (Lausanne), 2020, 11: 386.
30.	Park MD, Silvin A, Ginhoux F, et al. Macrophages in health and disease. Cell, 2022, 185(23): 4259-4279.
31.	Tian G, Liu C, Gong Q, et al. Human umbilical cord mesenchymal stem cells improve the necrosis and osteocyte apoptosis in glucocorticoid-induced osteonecrosis of the femoral head model through reducing the macrophage polarization. Int J Stem Cells, 2022, 15(2): 195-202.
32.	Adapala NS, Yamaguchi R, Phipps M, et al. Necrotic bone stimulates proinflammatory responses in macrophages through the activation of toll-like receptor 4. Am J Pathol, 2016, 186(11): 2987-2999.
33.	Jiang C, Zhou Z, Lin Y, et al. Astragaloside Ⅳ ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages. Int Immunopharmacol, 2021, 93: 107345.
34.	Motta F, Timilsina S, Gershwin ME, et al. Steroid-induced osteonecrosis. J Transl Autoimmun, 2022, 5: 100168.
35.	Tan Z, Wang Y, Chen Y, et al. The dynamic feature of macrophage M1/M2 imbalance facilitates the progression of non-traumatic osteonecrosis of the femoral head. Front Bioeng Biotechnol, 2022, 10: 912133.
36.	Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol, 2013, 13(3): 159-175.
37.	Wu X, Xu W, Feng X, et al. TNF-a mediated inflammatory macrophage polarization contributes to the pathogenesis of steroid-induced osteonecrosis in mice. Int J Immunopathol Pharmacol, 2015, 28(3): 351-361.
38.	Kaneko J, Okinaga T, Hikiji H, et al. Zoledronic acid exacerbates inflammation through M1 macrophage polarization. Inflamm Regen, 2018, 38: 16.
39.	Rose-John S. Interleukin-6 family cytokines. Cold Spring Harb Perspect Biol, 2018, 10(2): a028415.
40.	Wang T, He C. TNF-α and IL-6: The link between immune and bone system. Curr Drug Targets, 2020, 21(3): 213-227.
41.	Kuroyanagi G, Adapala NS, Yamaguchi R, et al. Interleukin-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis in a murine model. Bone, 2018, 116: 221-231.
42.	Zhou Z, Pan C, Wang N, et al. A high-fat diet aggravates osteonecrosis through a macrophage-derived IL-6 pathway. Int Immunol, 2019, 31(4): 263-273.
43.	Yao Z, Getting SJ, Locke IC. Regulation of TNF-induced osteoclast differentiation. Cells, 2021, 11(1): 132.
44.	Lisignoli G, Cristino S, Toneguzzi S, et al. IL1beta and TNFalpha differently modulate CXCL13 chemokine in stromal cells and osteoblasts isolated from osteoarthritis patients: evidence of changes associated to cell maturation. Exp Gerontol, 2004, 39(4): 659-665.
45.	Okazaki S, Nagoya S, Matsumoto H, et al. TLR4 stimulation and corticosteroid interactively induce osteonecrosis of the femoral head in rat. J Orthop Res, 2016, 34(2): 342-345.
46.	Zhu D, Yu H, Liu P, et al. Calycosin modulates inflammation via suppressing TLR4/NF-κB pathway and promotes bone formation to ameliorate glucocorticoid-induced osteonecrosis of the femoral head in rat. Phytother Res, 2021, 35(5): 2824-2835.
47.	Pei J, Fan L, Nan K, et al. Excessive activation of TLR4/NF-κB interactively suppresses the canonical Wnt/β-catenin pathway and induces SANFH in SD rats. Sci Rep, 2017, 7(1): 11928.
48.	Jin S, Meng C, He Y, et al. Curcumin prevents osteocyte apoptosis by inhibiting M1-type macrophage polarization in mice model of glucocorticoid-associated osteonecrosis of the femoral head. J Orthop Res, 2020, 38(9): 2020-2030.
49.	Lan X, Yu R, Xu J, et al. Exosomes from chondrocytes overexpressing miR-214-3p facilitate M2 macrophage polarization and angiogenesis to relieve Legg-Calvé-Perthes disease. Cytokine, 2023, 168: 156233.
50.	Chen C, Fu L, Luo Y, et al. Engineered exosome-functionalized extracellular matrix-mimicking hydrogel for promoting bone repair in glucocorticoid-induced osteonecrosis of the femoral head. ACS Appl Mater Interfaces, 2023, 15(24): 28891-28906.
51.	Kerneur C, Cano CE, Olive D. Major pathways involved in macrophage polarization in cancer. Front Immunol, 2022, 13: 1026954.
52.	Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol, 2018, 233(9): 6425-6440.
53.	Zou D, Zhang K, Yang Y, et al. Th17 and IL-17 exhibit higher levels in osteonecrosis of the femoral head and have a positive correlation with severity of pain. Endokrynol Pol, 2018, 69(3): 283-290.
54.	Nonokawa M, Shimizu T, Yoshinari M, et al. Association of neutrophil extracellular traps with the development of idiopathic osteonecrosis of the femoral head. Am J Pathol, 2020, 190(11): 2282-2289.
55.	Chen C, Zhao X, Luo Y, et al. Imbalanced T-cell subsets may facilitate the occurrence of osteonecrosis of the femoral head. J Inflamm Res, 2022, 15: 4159-4169.

1. Meng K, Liu Y, Ruan L, et al. Suppression of apoptosis in osteocytes, the potential way of natural medicine in the treatment of osteonecrosis of the femoral head. Biomed Pharmacother, 2023, 162: 114403.
2. Zheng J, Yao Z, Xue L, et al. The role of immune cells in modulating chronic inflammation and osteonecrosis. Front Immunol, 2022, 13: 1064245.
3. Quan H, Ren C, He Y, et al. Application of biomaterials in treating early osteonecrosis of the femoral head: Research progress and future perspectives. Acta biomaterialia, 2023, 164: 15-73.
4. Lou P, Zhou G, Wei B, et al. Sclerotic zone in femoral head necrosis: from pathophysiology to therapeutic implications. EFORT Open Reviews, 2023, 8(6): 451-458.
5. Wang J, Xu P, Zhou L. Comparison of current treatment strategy for osteonecrosis of the femoral head from the perspective of cell therapy. Front Cell Dev Biol, 2023, 11: 995816.
6. Che Z, Song Y, Zhu L, et al. Emerging roles of growth factors in osteonecrosis of the femoral head. Front Genet, 2022, 13: 1037190.
7. Wang X, Chen X, Lu L, et al. Alcoholism and osteoimmunology. Curr Med Chem, 2021, 28(9): 1815-1828.
8. Tsukasaki M, Takayanagi H. Osteoimmunology: evolving concepts in bone-immune interactions in health and disease. Nat Rev Immunol, 2019, 19(10): 626-642.
9. Saxena Y, Routh S, Mukhopadhaya A. Immunoporosis: role of innate immune cells in osteoporosis. Front Immunol, 2021, 12: 687037.
10. Yang N, Liu Y. The role of the immune microenvironment in bone regeneration. Int J Med Sci, 2021, 18(16): 3697-3707.
11. Vicaş RM, Bodog FD, Fugaru FO, et al. Histopathological and immunohistochemical aspects of bone tissue in aseptic necrosis of the femoral head. Rom J Morphol Embryol, 2020, 61(4): 1249-1258.
12. Liang XZ, Liu XC, Li S, et al. IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head. J Orthop Surg Res, 2023, 18(1): 27.
13. Wang B, Gong S, Shao W, et al. Comprehensive analysis of pivotal biomarkers, immune cell infiltration and therapeutic drugs for steroid-induced osteonecrosis of the femoral head. Bioengineered, 2021, 12(1): 5971-5984.
14. Yu R, Zhang J, Zhuo Y, et al. ARG2, MAP4K5 and TSTA3 as diagnostic markers of steroid-induced osteonecrosis of the femoral head and their correlation with immune infiltration. Front Genet, 2021, 12: 691465.
15. Zhao J, Zhang X, Guan J, et al. Identification of key biomarkers in steroid-induced osteonecrosis of the femoral head and their correlation with immune infiltration by bioinformatics analysis. BMC Musculoskelet Disord, 2022, 23(1): 67.
16. Schlundt C, Fischer H, Bucher CH, et al. The multifaceted roles of macrophages in bone regeneration: A story of polarization, activation and time. Acta biomaterialia, 2021, 133: 46-57.
17. Yao Y, Cai X, Ren F, et al. The macrophage-osteoclast axis in osteoimmunity and osteo-related diseases. Front Immunol, 2021, 12: 664871.
18. Zhang Q, Sun W, Li T, et al. Polarization behavior of bone macrophage as well as associated osteoimmunity in glucocorticoid-induced osteonecrosis of the femoral head. J Inflamm Res, 2023, 16: 879-894.
19. Viola A, Munari F, Sánchez-Rodríguez R, et al. The metabolic signature of macrophage responses. Front Immunol, 2019, 10: 1462.
20. Wang C, Ma C, Gong L, et al. Macrophage polarization and its role in liver disease. Front Immunol, 2021, 12: 803037.
21. Davis FM, Gallagher KA. Epigenetic mechanisms in monocytes/macrophages regulate inflammation in cardiometabolic and vascular disease. Arterioscler Thromb Vasc Biol, 2019, 39(4): 623-634.
22. Orecchioni M, Ghosheh Y, Pramod AB, et al. Macrophage polarization: Different gene signatures in M1(LPS+) vs classically and M2(LPS-) vs alternatively activated macrophages. Front Immunol, 2019, 10: 1084.
23. Tang PM, Nikolic-Paterson DJ, Lan HY. Macrophages: versatile players in renal inflammation and fibrosis. Nat Rev Nephrol, 2019, 15(3): 144-158.
24. Gharavi AT, Hanjani NA, Movahed E, et al. The role of macrophage subtypes and exosomes in immunomodulation. Cell Mol Biol Lett, 2022, 27(1): 83.
25. Williams DW, Vuong HE, Kim S, et al. Indigenous microbiota protects against inflammation-induced osteonecrosis. J Dent Res, 2020, 99(6): 676-684.
26. Goodman SB, Maruyama M. Inflammation, bone healing and osteonecrosis: from bedside to bench. J Inflamm Res, 2020, 13: 913-923.
27. Loi F, Córdova LA, Pajarinen J, et al. Inflammation, fracture and bone repair. Bone, 2016, 86: 119-130.
28. ElHawary H, Baradaran A, Abi-Rafeh J, et al. Bone healing and inflammation: principles of fracture and repair. Semin Plast Surg, 2021, 35(3): 198-203.
29. Maruyama M, Rhee C, Utsunomiya T, et al. Modulation of the inflammatory response and bone healing. Front Endocrinol (Lausanne), 2020, 11: 386.
30. Park MD, Silvin A, Ginhoux F, et al. Macrophages in health and disease. Cell, 2022, 185(23): 4259-4279.
31. Tian G, Liu C, Gong Q, et al. Human umbilical cord mesenchymal stem cells improve the necrosis and osteocyte apoptosis in glucocorticoid-induced osteonecrosis of the femoral head model through reducing the macrophage polarization. Int J Stem Cells, 2022, 15(2): 195-202.
32. Adapala NS, Yamaguchi R, Phipps M, et al. Necrotic bone stimulates proinflammatory responses in macrophages through the activation of toll-like receptor 4. Am J Pathol, 2016, 186(11): 2987-2999.
33. Jiang C, Zhou Z, Lin Y, et al. Astragaloside Ⅳ ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages. Int Immunopharmacol, 2021, 93: 107345.
34. Motta F, Timilsina S, Gershwin ME, et al. Steroid-induced osteonecrosis. J Transl Autoimmun, 2022, 5: 100168.
35. Tan Z, Wang Y, Chen Y, et al. The dynamic feature of macrophage M1/M2 imbalance facilitates the progression of non-traumatic osteonecrosis of the femoral head. Front Bioeng Biotechnol, 2022, 10: 912133.
36. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol, 2013, 13(3): 159-175.
37. Wu X, Xu W, Feng X, et al. TNF-a mediated inflammatory macrophage polarization contributes to the pathogenesis of steroid-induced osteonecrosis in mice. Int J Immunopathol Pharmacol, 2015, 28(3): 351-361.
38. Kaneko J, Okinaga T, Hikiji H, et al. Zoledronic acid exacerbates inflammation through M1 macrophage polarization. Inflamm Regen, 2018, 38: 16.
39. Rose-John S. Interleukin-6 family cytokines. Cold Spring Harb Perspect Biol, 2018, 10(2): a028415.
40. Wang T, He C. TNF-α and IL-6: The link between immune and bone system. Curr Drug Targets, 2020, 21(3): 213-227.
41. Kuroyanagi G, Adapala NS, Yamaguchi R, et al. Interleukin-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis in a murine model. Bone, 2018, 116: 221-231.
42. Zhou Z, Pan C, Wang N, et al. A high-fat diet aggravates osteonecrosis through a macrophage-derived IL-6 pathway. Int Immunol, 2019, 31(4): 263-273.
43. Yao Z, Getting SJ, Locke IC. Regulation of TNF-induced osteoclast differentiation. Cells, 2021, 11(1): 132.
44. Lisignoli G, Cristino S, Toneguzzi S, et al. IL1beta and TNFalpha differently modulate CXCL13 chemokine in stromal cells and osteoblasts isolated from osteoarthritis patients: evidence of changes associated to cell maturation. Exp Gerontol, 2004, 39(4): 659-665.
45. Okazaki S, Nagoya S, Matsumoto H, et al. TLR4 stimulation and corticosteroid interactively induce osteonecrosis of the femoral head in rat. J Orthop Res, 2016, 34(2): 342-345.
46. Zhu D, Yu H, Liu P, et al. Calycosin modulates inflammation via suppressing TLR4/NF-κB pathway and promotes bone formation to ameliorate glucocorticoid-induced osteonecrosis of the femoral head in rat. Phytother Res, 2021, 35(5): 2824-2835.
47. Pei J, Fan L, Nan K, et al. Excessive activation of TLR4/NF-κB interactively suppresses the canonical Wnt/β-catenin pathway and induces SANFH in SD rats. Sci Rep, 2017, 7(1): 11928.
48. Jin S, Meng C, He Y, et al. Curcumin prevents osteocyte apoptosis by inhibiting M1-type macrophage polarization in mice model of glucocorticoid-associated osteonecrosis of the femoral head. J Orthop Res, 2020, 38(9): 2020-2030.
49. Lan X, Yu R, Xu J, et al. Exosomes from chondrocytes overexpressing miR-214-3p facilitate M2 macrophage polarization and angiogenesis to relieve Legg-Calvé-Perthes disease. Cytokine, 2023, 168: 156233.
50. Chen C, Fu L, Luo Y, et al. Engineered exosome-functionalized extracellular matrix-mimicking hydrogel for promoting bone repair in glucocorticoid-induced osteonecrosis of the femoral head. ACS Appl Mater Interfaces, 2023, 15(24): 28891-28906.
51. Kerneur C, Cano CE, Olive D. Major pathways involved in macrophage polarization in cancer. Front Immunol, 2022, 13: 1026954.
52. Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol, 2018, 233(9): 6425-6440.
53. Zou D, Zhang K, Yang Y, et al. Th17 and IL-17 exhibit higher levels in osteonecrosis of the femoral head and have a positive correlation with severity of pain. Endokrynol Pol, 2018, 69(3): 283-290.
54. Nonokawa M, Shimizu T, Yoshinari M, et al. Association of neutrophil extracellular traps with the development of idiopathic osteonecrosis of the femoral head. Am J Pathol, 2020, 190(11): 2282-2289.
55. Chen C, Zhao X, Luo Y, et al. Imbalanced T-cell subsets may facilitate the occurrence of osteonecrosis of the femoral head. J Inflamm Res, 2022, 15: 4159-4169.

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Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head

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