β-Hydroxybutyrate alleviates cartilage senescence through hnRNP A1-mediated up-regulation of PTEN

Senescence chondrocytes play an important role in Osteoarthritis (OA) progression. However, alleviating OA progression through senescent chondrocyte intervention still faces great challenges. β-Hydroxybutyrate (BHB) exhibits anti-senescence effects in a variety of age-related dis-eases, but its role...

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Main Authors: Guang Xia, Zi Wen, Lina Zhang, Junjie Huang, Xinxing Wang, Chi Liang, Xiaoyu Cui, Xu Cao, Song Wu
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Experimental Gerontology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S053155652300061X
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author Guang Xia
Zi Wen
Lina Zhang
Junjie Huang
Xinxing Wang
Chi Liang
Xiaoyu Cui
Xu Cao
Song Wu
author_facet Guang Xia
Zi Wen
Lina Zhang
Junjie Huang
Xinxing Wang
Chi Liang
Xiaoyu Cui
Xu Cao
Song Wu
author_sort Guang Xia
collection DOAJ
description Senescence chondrocytes play an important role in Osteoarthritis (OA) progression. However, alleviating OA progression through senescent chondrocyte intervention still faces great challenges. β-Hydroxybutyrate (BHB) exhibits anti-senescence effects in a variety of age-related dis-eases, but its role in osteoarthritis remains poorly understood. To explore the molecular mechanisms, gene sequencing was used to identify critical genes and potential cellular signaling pathways and male SD rats were used to generate an osteoarthritis model. Results showed that BHB attenuated the senescence of Osteoarthritis chondrocytes (OA-Chos) and alleviated OA progression. Gene ontology (GO) enrichment analysis revealed significant changes in cell cycle genes, with PTEN being the most significant differentially expressed gene. BHB up-regulated the expression of PTEN in OA-Chos, thereby alleviating chondrocyte senescence. Furthermore, BHB facilitated the expression of PTEN by binding to hnRNP A1 and inhibiting the phosphorylation of Akt. This study provided evidence that BHB mitigated chondrocyte senescence and delayed OA, and could thus be used as a novel therapeutic approach for osteoarthritis treatment.
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spelling doaj.art-a5fa94f9816a4231a6d56174de1a65432023-07-21T04:59:00ZengElsevierExperimental Gerontology1873-68152023-05-01175112140β-Hydroxybutyrate alleviates cartilage senescence through hnRNP A1-mediated up-regulation of PTENGuang Xia0Zi Wen1Lina Zhang2Junjie Huang3Xinxing Wang4Chi Liang5Xiaoyu Cui6Xu Cao7Song Wu8Department of Orthopaedics of the 3rd Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Orthopaedics of the 3rd Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Orthopaedics of the 3rd Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Orthopaedics of the 3rd Xiangya Hospital, Central South University, Changsha 410013, China; Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, ChinaDepartment of Orthopaedics of the 3rd Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Orthopaedics of the 3rd Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Anesthesiology of the 3rd Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Orthopaedics of the 3rd Xiangya Hospital, Central South University, Changsha 410013, China; Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Correspondence to: X. Cao, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.Department of Orthopaedics of the 3rd Xiangya Hospital, Central South University, Changsha 410013, China; Corresponding author.Senescence chondrocytes play an important role in Osteoarthritis (OA) progression. However, alleviating OA progression through senescent chondrocyte intervention still faces great challenges. β-Hydroxybutyrate (BHB) exhibits anti-senescence effects in a variety of age-related dis-eases, but its role in osteoarthritis remains poorly understood. To explore the molecular mechanisms, gene sequencing was used to identify critical genes and potential cellular signaling pathways and male SD rats were used to generate an osteoarthritis model. Results showed that BHB attenuated the senescence of Osteoarthritis chondrocytes (OA-Chos) and alleviated OA progression. Gene ontology (GO) enrichment analysis revealed significant changes in cell cycle genes, with PTEN being the most significant differentially expressed gene. BHB up-regulated the expression of PTEN in OA-Chos, thereby alleviating chondrocyte senescence. Furthermore, BHB facilitated the expression of PTEN by binding to hnRNP A1 and inhibiting the phosphorylation of Akt. This study provided evidence that BHB mitigated chondrocyte senescence and delayed OA, and could thus be used as a novel therapeutic approach for osteoarthritis treatment.http://www.sciencedirect.com/science/article/pii/S053155652300061Xβ-HydroxybutyrateSenescentOsteoarthritisPhosphatase and tensin homolog
spellingShingle Guang Xia
Zi Wen
Lina Zhang
Junjie Huang
Xinxing Wang
Chi Liang
Xiaoyu Cui
Xu Cao
Song Wu
β-Hydroxybutyrate alleviates cartilage senescence through hnRNP A1-mediated up-regulation of PTEN
Experimental Gerontology
β-Hydroxybutyrate
Senescent
Osteoarthritis
Phosphatase and tensin homolog
title β-Hydroxybutyrate alleviates cartilage senescence through hnRNP A1-mediated up-regulation of PTEN
title_full β-Hydroxybutyrate alleviates cartilage senescence through hnRNP A1-mediated up-regulation of PTEN
title_fullStr β-Hydroxybutyrate alleviates cartilage senescence through hnRNP A1-mediated up-regulation of PTEN
title_full_unstemmed β-Hydroxybutyrate alleviates cartilage senescence through hnRNP A1-mediated up-regulation of PTEN
title_short β-Hydroxybutyrate alleviates cartilage senescence through hnRNP A1-mediated up-regulation of PTEN
title_sort β hydroxybutyrate alleviates cartilage senescence through hnrnp a1 mediated up regulation of pten
topic β-Hydroxybutyrate
Senescent
Osteoarthritis
Phosphatase and tensin homolog
url http://www.sciencedirect.com/science/article/pii/S053155652300061X
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