Stromal Cell-Derived Factor 1α Inhibits Chondrocyte Apoptosis and Promotes Autophagy Through the Akt Signaling Pathway

LI Jiazhou, XIE Jing, ZHOU Xuedong

Abstract

To investigate the effects of stromal cell-derived factor 1α (SDF-1α) on the apoptosis and autophagy of chondrocytes and the underlying mechanisms.Methods Chondrocytes were isolated from the knee joints of neonatal mice. The chondrocytes were then stimulated with 0 (the control group), 50, 100, and 200 ng/mL of SDF-1α. CCK-8 assay was performed to determine the effects of SDF-1α stimulation for 24 h, 48 h, and 72 h on the viability of the chondrocytes. Wound healing assay was conducted to determine the effects of SDF-1α stimulation for 12 h and 24 h on chondrocyte migration. The changes in the expression of Akt signaling pathway proteins in chondrocytes were determined by Western blot assay. Chondrocytes were stimulated with 0 (the control group) and 200 ng/mL of SDF-1α. Flow cytometry was performed to determine the effect of SDF-1α on the apoptosis of chondrocytes. Transmission electron microscope was used to examine the effect of SDF-1α on chondrocyte autophagy. Immunofluorescence staining assays were performed to visualize the differences in p-Akt expression and distribution in chondrocytes treated with SDF-1α.Results Compared with the control group, findings for the experimental groups showed that SDF-1α at the concentrations of 50, 100, and 200 ng/mL did not decrease chondrocyte activity at any time point (P<0.01) and it consistently promoted chondrocyte migration at 24 h (P<0.05). Western blot results revealed that, in comparison to the control group, SDF-1α at concentrations of 50, 100, and 200 ng/mL significantly up-regulated the protein expression of p-Akt in chondrocytes, while no significant difference in Akt expression was observed. Flow cytometry demonstrated that SDF-1α could inhibit chondrocyte apoptosis (P<0.05) and transmission electron microscopic observation showed that SDF-1α promoted chondrocyte autophagy (P<0.05). Immunofluorescence staining showed that the expression of p-Akt in chondrocytes was concentrated in the perinuclear area of the cells and this expression was further enhanced in the perinuclear area of the chondrocytes after treatment with SDF-1α.Conclusion SDF-1α inhibits chondrocyte apoptosis and promotes chondrocyte migration and autophagy through activating the Akt signaling pathway.


Keywords: Stromal cell-derived factor 1α,  Chondrocyte,  Apoptosis,  Akt,  Autophagy   

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References


SAFIRI S， KOLAHI A A， SMITH E， et al. Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the global burden of disease study 2017. Ann Rheum Dis，2020，79(6): 819–828. doi: 10.1136/annrheumdis-2019-216515.

HUANG H C， WEI J Y， ZHANG D M， et al. Research progress of fibroblast growth factor 8's role in the regulation of bone development and homeostasis. J Sichuan Univ (Med Sci)，2022，53(1): 54–57. doi: 10. 12182/20220160509.

FELSON D T. Risk factors for osteoarthritis: understanding joint vulnerability. Clin Orthop Relat Res，2004，427(Suppl): S16–S21. doi: 10. 1097/01.blo.0000144971.12731.a2.

SUN K， LUO J， GUO J， et al. The PI3K/AKT/MTOR signaling pathway in osteoarthritis: a narrative review. Osteoarthritis Cartilage，2020，28(4): 400–409. doi: 10.1016/j.joca.2020.02.027.

NELSON A E. Osteoarthritis year in review 2017: clinical. Osteoarthritis Cartilage，2018，26(3): 319–325. doi: 10.1016/j.joca.2017.11.014.

ZHANG Z， YUAN L， LIU Y， et al. Integrated cascade nanozyme remodels chondrocyte inflammatory microenvironment in temporomandibular joint osteoarthritis via inhibiting ROS-NF-κB and mapk pathways. Adv Healthc Mater，2023，12(10): e2203195. doi: 10. 1002/adhm.202203195.

PAWIG L， KLASEN C， WEBER C， et al. Diversity and inter-connections in the cxcr4 chemokine receptor/ligand family: Molecular perspectives. Front Immunol，2015，6: 429. doi: 10.3389/fimmu.2015. 00429.

MURPHY P M， HEUSINKVELD L. Multisystem multitasking by CXCL12 and its receptors CXCR4 and ACKR3. Cytokine，2018，109: 2–10. doi: 10.1016/j.cyto.2017.12.022.

MENG Z， FENG G， HU X， et al. SDF factor-1α promotes the migration, proliferation, and osteogenic differentiation of mouse bone marrow mesenchymal stem cells through the WNT/β-catenin pathway. Stem Cells Dev，2021，30(2): 106–117. doi: 10.1089/scd.2020.0165.

CHEN Y， WU T， HUANG S， et al. Sustained release SDF-1α/TGF-β1-loaded silk fibroin-porous gelatin scaffold promotes cartilage repair. ACS Appl Mater Interfaces，2019，11(16): 14608–14618. doi: 10.1021/acsami. 9b01532.

DONG Y， LIU H， ZHANG X， et al. Inhibition of SDF-1alpha/CXCR4 signalling in subchondral bone attenuates post-traumatic osteoarthritis. Int J Mol Sci，2016，17(6): 943. doi: 10.3390/ijms17060943.

JARRAH A A， SCHWARSKOPF M， WANG E R， et al. Sdf-1 induces tnf-mediated apoptosis in cardiac myocytes. Apoptosis，2018，23(1): 79–91. doi: 10.1007/s10495-017-1438-3.

LI J， CHEN H， CAI L， et al. SDF-1α promotes chondrocyte autophagy through CXCR4/mtor signaling axis. Int J Mol Sci，2023，24(2): 1710. doi: 10.3390/ijms24021710.

SHACHAR I， KARIN N. The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications. J Leukoc Biol，2013，93(1): 51–61. doi: 10.1189/jlb.0612293.

KANBE K， TAKAGISHI K， CHEN Q. Stimulation of matrix metalloprotease 3 release from human chondrocytes by the interaction of stromal cell-derived factor 1 and CXC chemokine receptor 4. Arthritis Rheum，2002，46(1): 130–137. doi: 10.1002/1529-0131(200201)46:1<130:: aid-art10020>3.0.co;2-d.

LI J C， ZHANG D M， XIE J， et al. Co-culturing of osteoblasts and chondrocytes upregulates HIF-1 pathway of chondrocytes via MAPK signaling. J Sichuan Univ (Med Sci)，2022，53(1): 92–97. doi: 10.12182/ 20220160104.

WANG X Y， DU X M， ZHOU X D. New developments in research on the relationship between osteoarthritis and oral-gut microbes. J Sichuan Univ (Med Sci)，2023，54(1): 49–53. doi: 10.12182/20230160508.

XU S Q， WEI J Y， XIE J， et al. The role of platelet-derived growth factor-AA in the pathogenesis and development of osteoarthritis. J Sichuan Univ (Med Sci)，2022，53(2): 349–354. doi: 10.12182/20211260201.

TANG X， WANG S， ZHAN S， et al. The Prevalence of Symptomatic Knee Osteoarthritis in China: Results From the China Health and Retirement Longitudinal Study. Arthritis Rheumatol，2016，68(3): 648–653. doi: 10.1002/art.39465.

ZHANG Z， HUANG C， JIANG Q， et al. Guidelines for the diagnosis and treatment of osteoarthritis in China (2019 edition). Ann Transl Med， 2020，8(19): 1213. doi: 10.21037/atm-20-4665.

WU Y， LI J， ZENG Y， et al. Exosomes rewire the cartilage microenvironment in osteoarthritis: from intercellular communication to therapeutic strategies. Int J Oral Sci，2022，14(1): 40. doi: 10.1038/s41368-022-00187-z.

LI J， CHEN H， ZHANG D， et al. The role of stromal cell-derived factor 1 on cartilage development and disease. Osteoarthritis Cartilage，2021， 29(3): 313–322. doi: 10.1016/j.joca.2020.10.010.

ONUORA S. Osteoarthritis: chondrocyte clock maintains cartilage tissue. Nat Rev Rheumatol，2016，12(2): 71. doi: 10.1038/nrrheum.2015.183.

HÉRAUD F， HÉRAUD A， HARMAND M F. Apoptosis in normal and osteoarthritic human articular cartilage. Ann Rheum Dis，2000，59(12): 959–965. doi: 10.1136/ard.59.12.959.

HASHIMOTO S， OCHS R L， KOMIYA S， et al. Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum，1998，41(9): 1632–1638. doi: 10.1002/1529-0131(199809)41:9 <1632::Aid-art14>3.0.Co;2-a.

UO Q， CHEN X， CHEN J， et al. Sting promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the nf-κb signaling pathway. Cell Death Dis，2021，12(1): 13. doi: 10.1038/s41419-


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