S W Lee1, J H Rho2, S Y Lee3, J H Kim4, J-H Cheong5, H Y Kim6, N Y Jeong7, W T Chung8, Y H Yoo9. 1. Division of Rheumatology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea. Electronic address: leesw@dau.ac.kr. 2. Division of Rheumatology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea; Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, South Korea. Electronic address: rogiken@hanmail.net. 3. Division of Rheumatology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea. Electronic address: leesy@dau.ac.kr. 4. Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, South Korea; BK21 Plus Research Group, Longevity and Marine Biotechnology, College of Natural Sciences, Pusan National University, Busan, South Korea. Electronic address: freemj0629@naver.com. 5. BK21 Plus Research Group, Longevity and Marine Biotechnology, College of Natural Sciences, Pusan National University, Busan, South Korea. Electronic address: molecule85@pusan.ac.kr. 6. Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, South Korea. Electronic address: dolph02@dau.ac.kr. 7. Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, South Korea. Electronic address: jnyjjy@dau.ac.kr. 8. Division of Rheumatology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea. Electronic address: wtchung@dau.ac.kr. 9. Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, South Korea. Electronic address: yhyoo@dau.ac.kr.
Abstract
OBJECTIVE: Although leptin appears to be an important local and systemic factor influencing cartilage homeostasis, the role of leptin in chondrocyte death is largely unknown. Tumor necrosis factor α (TNF-α) is a pro-inflammatory cytokine that plays a central role in the pathogenesis of articular diseases. This study examines whether leptin modulates TNF-α-induced articular chondrocyte death. METHODS: Primary rat articular chondrocytes were isolated from knee joint cartilage slices. To induce cell death, the chondrocytes were treated with TNF-α. To examine whether leptin modulates the extent of TNF-α-mediated chondrocyte death, the cells were pretreated with leptin for 3 h before TNF-α treatment followed by viability analysis. To examine the mechanism by which leptin modulates the extent of TNF-α-mediated chondrocyte death, we utilized mitochondrial membrane potential (MMP) measurements, flow cytometry, nuclear morphology observation, co-immunoprecipitation, western blot analysis and confocal microscopy. RESULTS: We demonstrated that leptin suppresses TNF-α induced chondrocyte death. We further found that apoptosis partially contributes to TNF-α induced chondrocyte death while necroptosis primarily contributes to TNF-α induced chondrocyte death. In addition, we observed that leptin exerts anti-TNF-α toxicity via c-jun N-terminal kinase (JNK) in rat articular chondrocytes. CONCLUSION: Based on our findings, we suggest that the leptin present in the articular joint fluid protects articular chondrocytes against cumulative mechanical load and detrimental stresses throughout a lifetime, delaying the onset of degenerative changes in chondrocytes. We can further hypothesize that leptin protects articular chondrocytes against destructive stimuli even in the joints of osteoarthritis (OA) patients.
OBJECTIVE: Although leptin appears to be an important local and systemic factor influencing cartilage homeostasis, the role of leptin in chondrocyte death is largely unknown. Tumor necrosis factor α (TNF-α) is a pro-inflammatory cytokine that plays a central role in the pathogenesis of articular diseases. This study examines whether leptin modulates TNF-α-induced articular chondrocyte death. METHODS: Primary rat articular chondrocytes were isolated from knee joint cartilage slices. To induce cell death, the chondrocytes were treated with TNF-α. To examine whether leptin modulates the extent of TNF-α-mediated chondrocyte death, the cells were pretreated with leptin for 3 h before TNF-α treatment followed by viability analysis. To examine the mechanism by which leptin modulates the extent of TNF-α-mediated chondrocyte death, we utilized mitochondrial membrane potential (MMP) measurements, flow cytometry, nuclear morphology observation, co-immunoprecipitation, western blot analysis and confocal microscopy. RESULTS: We demonstrated that leptin suppresses TNF-α induced chondrocyte death. We further found that apoptosis partially contributes to TNF-α induced chondrocyte death while necroptosis primarily contributes to TNF-α induced chondrocyte death. In addition, we observed that leptin exerts anti-TNF-α toxicity via c-jun N-terminal kinase (JNK) in rat articular chondrocytes. CONCLUSION: Based on our findings, we suggest that the leptin present in the articular joint fluid protects articular chondrocytes against cumulative mechanical load and detrimental stresses throughout a lifetime, delaying the onset of degenerative changes in chondrocytes. We can further hypothesize that leptin protects articular chondrocytes against destructive stimuli even in the joints of osteoarthritis (OA) patients.
Authors: Alfonso Cordero-Barreal; María González-Rodríguez; Clara Ruiz-Fernández; Djedjiga Ait Eldjoudi; Yousof Ramadan Farrag AbdElHafez; Francisca Lago; Javier Conde; Rodolfo Gómez; Miguel Angel González-Gay; Ali Mobasheri; Jesus Pino; Oreste Gualillo Journal: Int J Mol Sci Date: 2021-02-27 Impact factor: 5.923
Authors: Sung Won Lee; Jee Hyun Rho; Sang Yeob Lee; Seung Hee Yoo; Hye Young Kim; Won Tae Chung; Young Hyun Yoo Journal: PLoS One Date: 2016-11-16 Impact factor: 3.240