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Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway

OBJECTIVE: To clarify the regulatory effect of Calcyclin (S100A6) on chondrocytes apoptosis and its relationship with progression of osteoarthritis in an effort to explore potential therapeutic targets for osteoarthritis. METHOD: Immunofluorescence assay was produced to identify the rat chondrocyte...

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Autores principales: Zhang, Xiao‐fei, Ma, Jian‐xiong, Wang, Yuan‐lin, Ma, Xin‐long
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126894/
https://www.ncbi.nlm.nih.gov/pubmed/33942537
http://dx.doi.org/10.1111/os.12990
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author Zhang, Xiao‐fei
Ma, Jian‐xiong
Wang, Yuan‐lin
Ma, Xin‐long
author_facet Zhang, Xiao‐fei
Ma, Jian‐xiong
Wang, Yuan‐lin
Ma, Xin‐long
author_sort Zhang, Xiao‐fei
collection PubMed
description OBJECTIVE: To clarify the regulatory effect of Calcyclin (S100A6) on chondrocytes apoptosis and its relationship with progression of osteoarthritis in an effort to explore potential therapeutic targets for osteoarthritis. METHOD: Immunofluorescence assay was produced to identify the rat chondrocyte sample and western blots assay was detected the expression changes of S100A6 between control group and osteoarthritis model which induced by interleukin‐1β. Adenovirus were transfected into the chondrocytes in vitro, in order to regulate the S100A6 expression. The influence of S100A6 on inflammatory reaction of osteoarthritis was detected by RT‐PCR. Also, Caspase‐3 activity assay and TUNEL assay were performed to evaluate the apoptosis changes. In addition, RT‐PCR and western blots were performed to verify that S100A6 mediated the PI3K/AKT signaling pathway. Through the usage of pathway regulator, we detected S100A6 produced the effect by mediating the PI3K/AKT pathway. RESULTS: We determined the expression of S100A6 decreased in osteoarthritis model, the relative expression level in osteoarthritis model was about 0.5 fold compared with control group. Through adenovirus transfection we revealed that the inflammatory factors of osteoarthritis (interleukin‐6 and matrix metalloproteinase‐13) showed a negative correlation with the S100A6 expression. The relative expression level of interleukin‐6 and matrix metalloproteinase‐13 were 1.534 and 1.259 when S100A6 was up‐regulated and the values were up to 2.445 and 2.074, respectively, when S100A6 was down‐regulated. Also, the data verified the apoptosis could be reduced when the S100A6 was up‐regulated and be activated when the S100A6 was down‐regulated, the Caspase‐3 activity was 16.512 U/μg and 24.45 U/μg respectively. Similar results were shown in TUNEL assay, the apoptosis index was 4.46% and 31.44%, respectively. Additionally, the results of polymerase chain reaction and western blots both demonstrated that the expression level of PI3K and AKT were increased when S100A6 was up‐regulated, conversely the expression level of those two signal modules were reduced if the S100A6 was down‐regulated. More importantly, the apoptosis triggered by S100A6 can be offset by the PI3K/AKT pathway inhibitor and activator (LY294002 and IGF‐1), the values of Caspase‐3 activity and apoptosis index became close to the untreated osteoarthritis group. The experimental results in this study were statistically significant. CONCLUSION: We investigated that Calcyclin (S100A6) relieved the inflammation and mediated the chondrocyte apoptosis through PI3K/AKT pathway and we confirmed that S100A6 might be an attractive therapeutic target.
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spelling pubmed-81268942021-05-21 Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway Zhang, Xiao‐fei Ma, Jian‐xiong Wang, Yuan‐lin Ma, Xin‐long Orthop Surg Scientific Articles OBJECTIVE: To clarify the regulatory effect of Calcyclin (S100A6) on chondrocytes apoptosis and its relationship with progression of osteoarthritis in an effort to explore potential therapeutic targets for osteoarthritis. METHOD: Immunofluorescence assay was produced to identify the rat chondrocyte sample and western blots assay was detected the expression changes of S100A6 between control group and osteoarthritis model which induced by interleukin‐1β. Adenovirus were transfected into the chondrocytes in vitro, in order to regulate the S100A6 expression. The influence of S100A6 on inflammatory reaction of osteoarthritis was detected by RT‐PCR. Also, Caspase‐3 activity assay and TUNEL assay were performed to evaluate the apoptosis changes. In addition, RT‐PCR and western blots were performed to verify that S100A6 mediated the PI3K/AKT signaling pathway. Through the usage of pathway regulator, we detected S100A6 produced the effect by mediating the PI3K/AKT pathway. RESULTS: We determined the expression of S100A6 decreased in osteoarthritis model, the relative expression level in osteoarthritis model was about 0.5 fold compared with control group. Through adenovirus transfection we revealed that the inflammatory factors of osteoarthritis (interleukin‐6 and matrix metalloproteinase‐13) showed a negative correlation with the S100A6 expression. The relative expression level of interleukin‐6 and matrix metalloproteinase‐13 were 1.534 and 1.259 when S100A6 was up‐regulated and the values were up to 2.445 and 2.074, respectively, when S100A6 was down‐regulated. Also, the data verified the apoptosis could be reduced when the S100A6 was up‐regulated and be activated when the S100A6 was down‐regulated, the Caspase‐3 activity was 16.512 U/μg and 24.45 U/μg respectively. Similar results were shown in TUNEL assay, the apoptosis index was 4.46% and 31.44%, respectively. Additionally, the results of polymerase chain reaction and western blots both demonstrated that the expression level of PI3K and AKT were increased when S100A6 was up‐regulated, conversely the expression level of those two signal modules were reduced if the S100A6 was down‐regulated. More importantly, the apoptosis triggered by S100A6 can be offset by the PI3K/AKT pathway inhibitor and activator (LY294002 and IGF‐1), the values of Caspase‐3 activity and apoptosis index became close to the untreated osteoarthritis group. The experimental results in this study were statistically significant. CONCLUSION: We investigated that Calcyclin (S100A6) relieved the inflammation and mediated the chondrocyte apoptosis through PI3K/AKT pathway and we confirmed that S100A6 might be an attractive therapeutic target. John Wiley & Sons Australia, Ltd 2021-05-04 /pmc/articles/PMC8126894/ /pubmed/33942537 http://dx.doi.org/10.1111/os.12990 Text en © 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Scientific Articles
Zhang, Xiao‐fei
Ma, Jian‐xiong
Wang, Yuan‐lin
Ma, Xin‐long
Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway
title Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway
title_full Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway
title_fullStr Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway
title_full_unstemmed Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway
title_short Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway
title_sort calcyclin (s100a6) attenuates inflammatory response and mediates apoptosis of chondrocytes in osteoarthritis via the pi3k/akt pathway
topic Scientific Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126894/
https://www.ncbi.nlm.nih.gov/pubmed/33942537
http://dx.doi.org/10.1111/os.12990
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