Research progress on the ceramide-1-phosphate signal pathway and the pathogenesis of osteoarthritis_West China Medical Journal

Authors：

HAN Huaimin ¹ ,  LIU Rui ²

1. Graduate School of Inner Mongolia Medical University, Hohhot, Inner Mongolia 10010, P. R. China;
2. Department of Orthopedics, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 10010, P. R. China;

Corresponding author：

LIU Rui, Email: liuruifl88@163.com

Keywords：

Osteoarthritis; ceramide-1-phosphate; pathogenesis; immune cell

DOI：

10.7507/1002-0179.202505009

Video：

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Osteoarthritis (OA) is a degenerative joint disease characterized by redness, swelling, heat, pain, functional impairment, and joint deformities. In severe cases, it can lead to joint disability and affect quality of life. However, the pathogenesis of OA is still unclear, but studies have shown that the signaling pathway dominated by ceramide-1-phosphate can lead to joint pain, inflammation, and degeneration. Therefore, this article summarizes and analyzes the pathogenesis of OA dominated by the ceramide-1-phosphate signaling pathway, aiming to provide references for future research.

Citation： HAN Huaimin, LIU Rui. Research progress on the ceramide-1-phosphate signal pathway and the pathogenesis of osteoarthritis. West China Medical Journal, 2026, 41(1): 155-158. doi: 10.7507/1002-0179.202505009 Copy

1.	李盈宏, 王雅慧, 姜益常, 等. 针刀疗法治疗膝骨关节炎的作用机制及研究进展. 华西医学, 2025, 40(4): 665-670.
2.	马拓. 骨关节炎: 了解、预防与治疗的全面指南. 健康必读, 2025(12): 116, 115.
3.	张倩, 黄东锋. 加权基因共表达网络分析结合机器学习筛选及验证骨关节炎生物标记物. 中国组织工程研究, 2026, 30(5): 1096-1105.
4.	李健伟, 胡锋, 殷琴, 等. 大黄酚对骨关节炎大鼠软骨损伤的影响及其机制的探讨. 中国免疫学杂志, 2025, 41(4): 808-814.
5.	袁传健, 王羽彤, 梁延琛. 创伤后骨关节炎中软骨细胞死亡途径的研究进展. 临床骨科杂志, 2025, 28(2): 297-301.
6.	Jahn S, Seror J, Klein J. Lubrication of articular cartilage. Annu Rev Biomed Eng, 2016, 18: 235-258.
7.	Kim MK, Lee HY, Park KS, et al. Lysophosphatidic acid stimulates cell proliferation in rat chondrocytes. Biochem Pharmacol, 2005, 70(12): 1764-1771.
8.	Pousinis P, Gowler PRW, Burston JJ, et al. Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis. Metabolomics, 2020, 16(3): 32.
9.	Masuko K, Murata M, Nakamura H, et al. Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E2 from human articular chondrocytes. BMC Musculoskelet Disord, 2007, 8: 29.
10.	Jenei-Lanzl Z, Meurer A, Zaucke F. Interleukin-1β signaling in osteoarthritis - chondrocytes in focus. Cell Signal, 2019, 53: 212-223.
11.	Clockaerts S, Van Osch GJ, Bastiaansen-Jenniskens YM, et al. Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study. Ann Rheum Dis, 2012, 71(5): 642-647.
12.	Papathanasiou I, Anastasopoulou L, Tsezou A. Cholesterol metabolism related genes in osteoarthritis. Bone, 2021, 152: 116076.
13.	Buccitelli C, Selbach M. mRNAs, proteins and the emerging principles of gene expression control. Nat Rev Genet, 2020, 21(10): 630-644.
14.	Schwanhäusser B, Busse D, Li N, et al. Global quantification of mammalian gene expression control. Nature, 2011, 473(7347): 337-342.
15.	Rocha B, Cillero-Pastor B, Ruiz-Romero C, et al. Identification of a distinct lipidomic profile in the osteoarthritic synovial membrane by mass spectrometry imaging. Osteoarthritis Cartilage, 2021, 29(5): 750-761.
16.	Kosinska MK, Liebisch G, Lochnit G, et al. A lipidomic study of phospholipid classes and species in human synovial fluid. Arthritis Rheum, 2013, 65(9): 2323-2333.
17.	Granado MH, Gangoiti P, Ouro A, et al. Ceramide 1-phosphate (C1P) promotes cell migration involvement of a specific C1P receptor. Cell Signal, 2009, 21(3): 405-412.
18.	Cherifi C, Latourte A, Vettorazzi S, et al. Inhibition of sphingosine 1-phosphate protects mice against chondrocyte catabolism and osteoarthritis. Osteoarthritis Cartilage, 2021, 29(9): 1335-1345.
19.	Timm T, Hild C, Liebisch G, et al. Functional insights into the sphingolipids C1P, S1P, and SPC in human fibroblast-like synoviocytes by proteomic analysis. Int J Mol Sci, 2024, 25(15): 8363.
20.	Simanshu DK, Kamlekar RK, Wijesinghe DS, et al. Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids. Nature, 2013, 500(7463): 463-467.
21.	Dong W, Li Q, Lu X, et al. Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2. Exp Mol Med, 2024, 56(4): 946-958.
22.	Nixon GF. Sphingolipids in inflammation: pathological implications and potential therapeutic targets. Br J Pharmacol, 2009, 158(4): 982-993.
23.	Pettus BJ, Bielawska A, Subramanian P, et al. Ceramide 1-phosphate is a direct activator of cytosolic phospholipase A2. J Biol Chem, 2004, 279(12): 11320-11326.
24.	Ghidoni R, Caretti A, Signorelli P. Role of sphingolipids in the pathobiology of lung inflammation. Mediators Inflamm, 2015, 2015: 487508.
25.	Schütze S, Potthoff K, Machleidt T, et al. TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced “acidic” sphingomyelin breakdown. Cell, 1992, 71(5): 765-776.
26.	Dröge W. Free radicals in the physiological control of cell function. Physiol Rev, 2002, 82(1): 47-95.
27.	Gomez-Larrauri A, Benito-Vicente A, Larrea-Sebal A, et al. Role of ceramide kinase/C1P in the regulation of cell growth and survival. Int J Mol Sci, 2025, 26(17): 8374.
28.	Brigelius-Flohé R. Glutathione peroxidases and redox-regulated transcription factors. Biol Chem, 2006, 387(10/11): 1329-1335.
29.	Kim HG, Kim YR, Park JH, et al. Endosulfan induces COX-2 expression via NADPH oxidase and the ROS, MAPK, and Akt pathways. Arch Toxicol, 2015, 89(11): 2039-2050.
30.	Brinkmann V, Billich A, Baumruker T, et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov, 2010, 9(11): 883-897.
31.	Cao Y, Luo F, Peng J, et al. KMT2B-dependent RFK transcription activates the TNF-α/NOX2 pathway and enhances ferroptosis caused by myocardial ischemia-reperfusion. J Mol Cell Cardiol, 2022, 173: 75-91.
32.	Xu M, Zhang C, Han Y, et al. TNF-α promotes expression of inflammatory factors by upregulating nicotinamide adenine dinucleotide phosphate oxidase-2 expression in human gingival fibroblasts. J Dent Sci, 2024, 19(1): 211-219.
33.	张湛奇, 蔡永杰, 丁文倩, 等. N-乙酰转移酶 NAT10 通过 Nox2-ROS-NF-κB 调控巨噬细胞炎症反应//中华口腔医学会牙体牙髓病学专业委员. 中华口腔医学会牙体牙髓病学专业委员会第 17 次牙体牙髓病学学术会议摘要集. 广州: 中山大学光华口腔医学院附属口腔医院广东省口腔医学重点实验室, 2024: 347-349.
34.	Arra M, Abu-Amer Y. Cross-talk of inflammation and chondrocyte intracellular metabolism in osteoarthritis. Osteoarthritis Cartilage, 2023, 31(8): 1012-1021.
35.	蔡灵敏, 杨娅芹, 郭翱. 铜死亡相关基因 FDX1 调控骨关节炎软骨细胞增殖的分子机制研究. 浙江中西医结合杂志, 2025, 35(2): 112-120.
36.	Chang JW, Tang CH. The role of macrophage polarization in rheumatoid arthritis and osteoarthritis: pathogenesis and therapeutic strategies. Int Immunopharmacol, 2024, 142(Pt A): 113056.
37.	Xie JW, Wang Y, Xiao K, et al. Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization. Osteoarthritis Cartilage, 2021, 29(7): 1048-1059.
38.	杨双庆, 刘亚伟, 张苏丹, 等. miRNAs 调控骨关节炎软骨组织的研究进展. 国际老年医学杂志, 2023, 44(5): 621-624.
39.	Zhang Y, Jiao X, Wang T, et al. piRNA mmu_piR_037459 suppression alleviated the degeneration of chondrocyte and cartilage. Int Immunopharmacol, 2024, 128: 111473.
40.	Jiang T, Zhang J, Ruan B, et al. Trachelogenin alleviates osteoarthritis by inhibiting osteoclastogenesis and enhancing chondrocyte survival. Chin Med, 2024, 19(1): 37.
41.	Zhu W, Yang X, Liu S, et al. Lentivirus-based shRNA of caspase-3 gene silencing inhibits chondrocyte apoptosis and delays the progression of surgically induced osteoarthritis. Biotechnol J, 2024, 19(1): e2300031.
42.	Zhang X, Wang X, Yu F, et al. PiRNA hsa_piR_019949 promotes chondrocyte anabolic metabolism by inhibiting the expression of lncRNA NEAT1. J Orthop Surg Res, 2024, 19(1): 31.
43.	Kong H, Han JJ, Dmitrii G, et al. Phytochemicals against osteoarthritis by inhibiting apoptosis. Molecules, 2024, 29(7): 1487.
44.	史振华, 王晓萍, 周明旺, 等. microRNAs 介导的炎症相关信号通路调控骨性关节炎软骨细胞功能的研究进展. 现代医药卫生, 2025, 41(6): 1469-1474.

1. 李盈宏, 王雅慧, 姜益常, 等. 针刀疗法治疗膝骨关节炎的作用机制及研究进展. 华西医学, 2025, 40(4): 665-670.
2. 马拓. 骨关节炎: 了解、预防与治疗的全面指南. 健康必读, 2025(12): 116, 115.
3. 张倩, 黄东锋. 加权基因共表达网络分析结合机器学习筛选及验证骨关节炎生物标记物. 中国组织工程研究, 2026, 30(5): 1096-1105.
4. 李健伟, 胡锋, 殷琴, 等. 大黄酚对骨关节炎大鼠软骨损伤的影响及其机制的探讨. 中国免疫学杂志, 2025, 41(4): 808-814.
5. 袁传健, 王羽彤, 梁延琛. 创伤后骨关节炎中软骨细胞死亡途径的研究进展. 临床骨科杂志, 2025, 28(2): 297-301.
6. Jahn S, Seror J, Klein J. Lubrication of articular cartilage. Annu Rev Biomed Eng, 2016, 18: 235-258.
7. Kim MK, Lee HY, Park KS, et al. Lysophosphatidic acid stimulates cell proliferation in rat chondrocytes. Biochem Pharmacol, 2005, 70(12): 1764-1771.
8. Pousinis P, Gowler PRW, Burston JJ, et al. Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis. Metabolomics, 2020, 16(3): 32.
9. Masuko K, Murata M, Nakamura H, et al. Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E2 from human articular chondrocytes. BMC Musculoskelet Disord, 2007, 8: 29.
10. Jenei-Lanzl Z, Meurer A, Zaucke F. Interleukin-1β signaling in osteoarthritis - chondrocytes in focus. Cell Signal, 2019, 53: 212-223.
11. Clockaerts S, Van Osch GJ, Bastiaansen-Jenniskens YM, et al. Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study. Ann Rheum Dis, 2012, 71(5): 642-647.
12. Papathanasiou I, Anastasopoulou L, Tsezou A. Cholesterol metabolism related genes in osteoarthritis. Bone, 2021, 152: 116076.
13. Buccitelli C, Selbach M. mRNAs, proteins and the emerging principles of gene expression control. Nat Rev Genet, 2020, 21(10): 630-644.
14. Schwanhäusser B, Busse D, Li N, et al. Global quantification of mammalian gene expression control. Nature, 2011, 473(7347): 337-342.
15. Rocha B, Cillero-Pastor B, Ruiz-Romero C, et al. Identification of a distinct lipidomic profile in the osteoarthritic synovial membrane by mass spectrometry imaging. Osteoarthritis Cartilage, 2021, 29(5): 750-761.
16. Kosinska MK, Liebisch G, Lochnit G, et al. A lipidomic study of phospholipid classes and species in human synovial fluid. Arthritis Rheum, 2013, 65(9): 2323-2333.
17. Granado MH, Gangoiti P, Ouro A, et al. Ceramide 1-phosphate (C1P) promotes cell migration involvement of a specific C1P receptor. Cell Signal, 2009, 21(3): 405-412.
18. Cherifi C, Latourte A, Vettorazzi S, et al. Inhibition of sphingosine 1-phosphate protects mice against chondrocyte catabolism and osteoarthritis. Osteoarthritis Cartilage, 2021, 29(9): 1335-1345.
19. Timm T, Hild C, Liebisch G, et al. Functional insights into the sphingolipids C1P, S1P, and SPC in human fibroblast-like synoviocytes by proteomic analysis. Int J Mol Sci, 2024, 25(15): 8363.
20. Simanshu DK, Kamlekar RK, Wijesinghe DS, et al. Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids. Nature, 2013, 500(7463): 463-467.
21. Dong W, Li Q, Lu X, et al. Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2. Exp Mol Med, 2024, 56(4): 946-958.
22. Nixon GF. Sphingolipids in inflammation: pathological implications and potential therapeutic targets. Br J Pharmacol, 2009, 158(4): 982-993.
23. Pettus BJ, Bielawska A, Subramanian P, et al. Ceramide 1-phosphate is a direct activator of cytosolic phospholipase A2. J Biol Chem, 2004, 279(12): 11320-11326.
24. Ghidoni R, Caretti A, Signorelli P. Role of sphingolipids in the pathobiology of lung inflammation. Mediators Inflamm, 2015, 2015: 487508.
25. Schütze S, Potthoff K, Machleidt T, et al. TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced “acidic” sphingomyelin breakdown. Cell, 1992, 71(5): 765-776.
26. Dröge W. Free radicals in the physiological control of cell function. Physiol Rev, 2002, 82(1): 47-95.
27. Gomez-Larrauri A, Benito-Vicente A, Larrea-Sebal A, et al. Role of ceramide kinase/C1P in the regulation of cell growth and survival. Int J Mol Sci, 2025, 26(17): 8374.
28. Brigelius-Flohé R. Glutathione peroxidases and redox-regulated transcription factors. Biol Chem, 2006, 387(10/11): 1329-1335.
29. Kim HG, Kim YR, Park JH, et al. Endosulfan induces COX-2 expression via NADPH oxidase and the ROS, MAPK, and Akt pathways. Arch Toxicol, 2015, 89(11): 2039-2050.
30. Brinkmann V, Billich A, Baumruker T, et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov, 2010, 9(11): 883-897.
31. Cao Y, Luo F, Peng J, et al. KMT2B-dependent RFK transcription activates the TNF-α/NOX2 pathway and enhances ferroptosis caused by myocardial ischemia-reperfusion. J Mol Cell Cardiol, 2022, 173: 75-91.
32. Xu M, Zhang C, Han Y, et al. TNF-α promotes expression of inflammatory factors by upregulating nicotinamide adenine dinucleotide phosphate oxidase-2 expression in human gingival fibroblasts. J Dent Sci, 2024, 19(1): 211-219.
33. 张湛奇, 蔡永杰, 丁文倩, 等. N-乙酰转移酶 NAT10 通过 Nox2-ROS-NF-κB 调控巨噬细胞炎症反应//中华口腔医学会牙体牙髓病学专业委员. 中华口腔医学会牙体牙髓病学专业委员会第 17 次牙体牙髓病学学术会议摘要集. 广州: 中山大学光华口腔医学院附属口腔医院广东省口腔医学重点实验室, 2024: 347-349.
34. Arra M, Abu-Amer Y. Cross-talk of inflammation and chondrocyte intracellular metabolism in osteoarthritis. Osteoarthritis Cartilage, 2023, 31(8): 1012-1021.
35. 蔡灵敏, 杨娅芹, 郭翱. 铜死亡相关基因 FDX1 调控骨关节炎软骨细胞增殖的分子机制研究. 浙江中西医结合杂志, 2025, 35(2): 112-120.
36. Chang JW, Tang CH. The role of macrophage polarization in rheumatoid arthritis and osteoarthritis: pathogenesis and therapeutic strategies. Int Immunopharmacol, 2024, 142(Pt A): 113056.
37. Xie JW, Wang Y, Xiao K, et al. Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization. Osteoarthritis Cartilage, 2021, 29(7): 1048-1059.
38. 杨双庆, 刘亚伟, 张苏丹, 等. miRNAs 调控骨关节炎软骨组织的研究进展. 国际老年医学杂志, 2023, 44(5): 621-624.
39. Zhang Y, Jiao X, Wang T, et al. piRNA mmu_piR_037459 suppression alleviated the degeneration of chondrocyte and cartilage. Int Immunopharmacol, 2024, 128: 111473.
40. Jiang T, Zhang J, Ruan B, et al. Trachelogenin alleviates osteoarthritis by inhibiting osteoclastogenesis and enhancing chondrocyte survival. Chin Med, 2024, 19(1): 37.
41. Zhu W, Yang X, Liu S, et al. Lentivirus-based shRNA of caspase-3 gene silencing inhibits chondrocyte apoptosis and delays the progression of surgically induced osteoarthritis. Biotechnol J, 2024, 19(1): e2300031.
42. Zhang X, Wang X, Yu F, et al. PiRNA hsa_piR_019949 promotes chondrocyte anabolic metabolism by inhibiting the expression of lncRNA NEAT1. J Orthop Surg Res, 2024, 19(1): 31.
43. Kong H, Han JJ, Dmitrii G, et al. Phytochemicals against osteoarthritis by inhibiting apoptosis. Molecules, 2024, 29(7): 1487.
44. 史振华, 王晓萍, 周明旺, 等. microRNAs 介导的炎症相关信号通路调控骨性关节炎软骨细胞功能的研究进展. 现代医药卫生, 2025, 41(6): 1469-1474.

West China Medical Journal

Research progress on the ceramide-1-phosphate signal pathway and the pathogenesis of osteoarthritis

Abstract Full text Figures/Tables Video References Cited by

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