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. 針刀療法治療膝骨關節炎的作用機制及研究進展. 華西醫學, 2025, 40(4): 665-670.
2.	馬拓. 骨關節炎: 了解、預防與治療的全面指南. 健康必讀, 2025(12): 116, 115.
3.	張倩, 黃東鋒. 加權基因共表達網絡分析結合機器學習篩選及驗證骨關節炎生物標記物. 中國組織工程研究, 2026, 30(5): 1096-1105.
4.	李健偉, 胡鋒, 殷琴, 等. 大黃酚對骨關節炎大鼠軟骨損傷的影響及其機制的探討. 中國免疫學雜志, 2025, 41(4): 808-814.
5.	袁傳健, 王羽彤, 梁延琛. 創傷后骨關節炎中軟骨細胞死亡途徑的研究進展. 臨床骨科雜志, 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.	Schwanh?usser 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.	Dr?ge 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.	張湛奇, 蔡永杰, 丁文倩, 等. N-乙酰轉移酶 NAT10 通過 Nox2-ROS-NF-κB 調控巨噬細胞炎癥反應//中華口腔醫學會牙體牙髓病學專業委員. 中華口腔醫學會牙體牙髓病學專業委員會第 17 次牙體牙髓病學學術會議摘要集. 廣州: 中山大學光華口腔醫學院附屬口腔醫院廣東省口腔醫學重點實驗室, 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.	蔡靈敏, 楊婭芹, 郭翱. 銅死亡相關基因 FDX1 調控骨關節炎軟骨細胞增殖的分子機制研究. 浙江中西醫結合雜志, 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.	楊雙慶, 劉亞偉, 張蘇丹, 等. miRNAs 調控骨關節炎軟骨組織的研究進展. 國際老年醫學雜志, 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.	史振華, 王曉萍, 周明旺, 等. microRNAs 介導的炎癥相關信號通路調控骨性關節炎軟骨細胞功能的研究進展. 現代醫藥衛生, 2025, 41(6): 1469-1474.

1. 李盈宏, 王雅慧, 姜益常, 等. 針刀療法治療膝骨關節炎的作用機制及研究進展. 華西醫學, 2025, 40(4): 665-670.
2. 馬拓. 骨關節炎: 了解、預防與治療的全面指南. 健康必讀, 2025(12): 116, 115.
3. 張倩, 黃東鋒. 加權基因共表達網絡分析結合機器學習篩選及驗證骨關節炎生物標記物. 中國組織工程研究, 2026, 30(5): 1096-1105.
4. 李健偉, 胡鋒, 殷琴, 等. 大黃酚對骨關節炎大鼠軟骨損傷的影響及其機制的探討. 中國免疫學雜志, 2025, 41(4): 808-814.
5. 袁傳健, 王羽彤, 梁延琛. 創傷后骨關節炎中軟骨細胞死亡途徑的研究進展. 臨床骨科雜志, 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. Schwanh?usser 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. Dr?ge 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. 張湛奇, 蔡永杰, 丁文倩, 等. N-乙酰轉移酶 NAT10 通過 Nox2-ROS-NF-κB 調控巨噬細胞炎癥反應//中華口腔醫學會牙體牙髓病學專業委員. 中華口腔醫學會牙體牙髓病學專業委員會第 17 次牙體牙髓病學學術會議摘要集. 廣州: 中山大學光華口腔醫學院附屬口腔醫院廣東省口腔醫學重點實驗室, 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. 蔡靈敏, 楊婭芹, 郭翱. 銅死亡相關基因 FDX1 調控骨關節炎軟骨細胞增殖的分子機制研究. 浙江中西醫結合雜志, 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. 楊雙慶, 劉亞偉, 張蘇丹, 等. miRNAs 調控骨關節炎軟骨組織的研究進展. 國際老年醫學雜志, 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. 史振華, 王曉萍, 周明旺, 等. microRNAs 介導的炎癥相關信號通路調控骨性關節炎軟骨細胞功能的研究進展. 現代醫藥衛生, 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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