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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2023-05-01
|
Series: | Experimental Gerontology |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S053155652300061X |
_version_ | 1827897319288209408 |
---|---|
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. |
first_indexed | 2024-03-12T22:46:21Z |
format | Article |
id | doaj.art-a5fa94f9816a4231a6d56174de1a6543 |
institution | Directory Open Access Journal |
issn | 1873-6815 |
language | English |
last_indexed | 2024-03-12T22:46:21Z |
publishDate | 2023-05-01 |
publisher | Elsevier |
record_format | Article |
series | Experimental Gerontology |
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 |
work_keys_str_mv | AT guangxia bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten AT ziwen bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten AT linazhang bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten AT junjiehuang bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten AT xinxingwang bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten AT chiliang bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten AT xiaoyucui bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten AT xucao bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten AT songwu bhydroxybutyratealleviatescartilagesenescencethroughhnrnpa1mediatedupregulationofpten |