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FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway
Introduction Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attri...
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Published in: | Journal of bone and mineral metabolism 2021-09, Vol.39 (5), p.769-779 |
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container_title | Journal of bone and mineral metabolism |
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creator | Zhang, Mengqi Wang, Yan Huan, Zhikun Liu, Yaping Zhang, Wenwen Kong, Dehuan Kong, Lei Xu, Jin |
description | Introduction
Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attributed to declining estrogen levels. Although follicle-stimulating hormone (FSH) levels become elevated in parallel, the effects of FSH on OA have been poorly explored. The present study aimed to study the effect of FSH on cartilage metabolism.
Methods
Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections.
Results
We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice.
Conclusions
Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator. |
doi_str_mv | 10.1007/s00774-021-01232-3 |
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Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attributed to declining estrogen levels. Although follicle-stimulating hormone (FSH) levels become elevated in parallel, the effects of FSH on OA have been poorly explored. The present study aimed to study the effect of FSH on cartilage metabolism.
Methods
Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections.
Results
We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice.
Conclusions
Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.</description><identifier>ISSN: 0914-8779</identifier><identifier>EISSN: 1435-5604</identifier><identifier>DOI: 10.1007/s00774-021-01232-3</identifier><identifier>PMID: 33988757</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Cartilage ; Cartilage (articular) ; Cartilage diseases ; Cell viability ; Chondrocytes ; Cyclic AMP response element-binding protein ; Degeneration ; Enzyme-linked immunosorbent assay ; Estrogens ; Extracellular matrix ; Follicle-stimulating hormone ; Immunofluorescence ; Joint diseases ; Medicine ; Medicine & Public Health ; Meniscus ; Menopause ; Metabolic Diseases ; Metabolism ; Original Article ; Orthopedics ; Osteoarthritis ; Post-menopause ; Protein kinase A ; Sox9 protein</subject><ispartof>Journal of bone and mineral metabolism, 2021-09, Vol.39 (5), p.769-779</ispartof><rights>The Japanese Society Bone and Mineral Research 2021</rights><rights>The Japanese Society Bone and Mineral Research 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-27552e64768b2231f02df9269986d31716154e76c43cee6ed9e8ec59b93deb243</citedby><cites>FETCH-LOGICAL-c399t-27552e64768b2231f02df9269986d31716154e76c43cee6ed9e8ec59b93deb243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33988757$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Mengqi</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Huan, Zhikun</creatorcontrib><creatorcontrib>Liu, Yaping</creatorcontrib><creatorcontrib>Zhang, Wenwen</creatorcontrib><creatorcontrib>Kong, Dehuan</creatorcontrib><creatorcontrib>Kong, Lei</creatorcontrib><creatorcontrib>Xu, Jin</creatorcontrib><title>FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway</title><title>Journal of bone and mineral metabolism</title><addtitle>J Bone Miner Metab</addtitle><addtitle>J Bone Miner Metab</addtitle><description>Introduction
Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attributed to declining estrogen levels. Although follicle-stimulating hormone (FSH) levels become elevated in parallel, the effects of FSH on OA have been poorly explored. The present study aimed to study the effect of FSH on cartilage metabolism.
Methods
Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections.
Results
We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice.
Conclusions
Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.</description><subject>Cartilage</subject><subject>Cartilage (articular)</subject><subject>Cartilage diseases</subject><subject>Cell viability</subject><subject>Chondrocytes</subject><subject>Cyclic AMP response element-binding protein</subject><subject>Degeneration</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Estrogens</subject><subject>Extracellular matrix</subject><subject>Follicle-stimulating hormone</subject><subject>Immunofluorescence</subject><subject>Joint diseases</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Meniscus</subject><subject>Menopause</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Osteoarthritis</subject><subject>Post-menopause</subject><subject>Protein kinase A</subject><subject>Sox9 protein</subject><issn>0914-8779</issn><issn>1435-5604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEURYMoWqt_wIUE3LgZm49JMllqaa1YUayCu5CZea0jM52aZJD-e6P1A1y4SQI5977HQeiIkjNKiBr4eKg0IYwmhDLOEr6FejTlIhGSpNuoRzRNk0wpvYf2vX8hhCqh6C7a41xnWXz30M14NsFNW3a1DVDiwrpQ1XYBeDS8wQ0Em7d15Rucr3GwbgGhWi5weAZ8d30-GN6PLgaz2yeNVzY8v9n1AdqZ29rD4dfdR4_j0cNwkkxvL6-G59Ok4FqHhCkhGMhUySxnjNM5YeVcM6l1JktOFZVUpKBkkfICQEKpIYNC6FzzEnKW8j463fSuXPvagQ-mqXwBdW2X0HbeMMEyqrTWKqInf9CXtnPLuF2kpNA8imORYhuqcK33DuZm5arGurWhxHzINhvZJso2n7INj6Hjr-oub6D8iXzbjQDfAD5-LRfgfmf_U_sOrFqGgg</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Zhang, Mengqi</creator><creator>Wang, Yan</creator><creator>Huan, Zhikun</creator><creator>Liu, Yaping</creator><creator>Zhang, Wenwen</creator><creator>Kong, Dehuan</creator><creator>Kong, Lei</creator><creator>Xu, Jin</creator><general>Springer Singapore</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20210901</creationdate><title>FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway</title><author>Zhang, Mengqi ; Wang, Yan ; Huan, Zhikun ; Liu, Yaping ; Zhang, Wenwen ; Kong, Dehuan ; Kong, Lei ; Xu, Jin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-27552e64768b2231f02df9269986d31716154e76c43cee6ed9e8ec59b93deb243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cartilage</topic><topic>Cartilage (articular)</topic><topic>Cartilage diseases</topic><topic>Cell viability</topic><topic>Chondrocytes</topic><topic>Cyclic AMP response element-binding protein</topic><topic>Degeneration</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Estrogens</topic><topic>Extracellular matrix</topic><topic>Follicle-stimulating hormone</topic><topic>Immunofluorescence</topic><topic>Joint diseases</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Meniscus</topic><topic>Menopause</topic><topic>Metabolic Diseases</topic><topic>Metabolism</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Osteoarthritis</topic><topic>Post-menopause</topic><topic>Protein kinase A</topic><topic>Sox9 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Mengqi</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Huan, Zhikun</creatorcontrib><creatorcontrib>Liu, Yaping</creatorcontrib><creatorcontrib>Zhang, Wenwen</creatorcontrib><creatorcontrib>Kong, Dehuan</creatorcontrib><creatorcontrib>Kong, Lei</creatorcontrib><creatorcontrib>Xu, Jin</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Mengqi</au><au>Wang, Yan</au><au>Huan, Zhikun</au><au>Liu, Yaping</au><au>Zhang, Wenwen</au><au>Kong, Dehuan</au><au>Kong, Lei</au><au>Xu, Jin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway</atitle><jtitle>Journal of bone and mineral metabolism</jtitle><stitle>J Bone Miner Metab</stitle><addtitle>J Bone Miner Metab</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>39</volume><issue>5</issue><spage>769</spage><epage>779</epage><pages>769-779</pages><issn>0914-8779</issn><eissn>1435-5604</eissn><abstract>Introduction
Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attributed to declining estrogen levels. Although follicle-stimulating hormone (FSH) levels become elevated in parallel, the effects of FSH on OA have been poorly explored. The present study aimed to study the effect of FSH on cartilage metabolism.
Methods
Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections.
Results
We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice.
Conclusions
Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>33988757</pmid><doi>10.1007/s00774-021-01232-3</doi><tpages>11</tpages></addata></record> |
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subjects | Cartilage Cartilage (articular) Cartilage diseases Cell viability Chondrocytes Cyclic AMP response element-binding protein Degeneration Enzyme-linked immunosorbent assay Estrogens Extracellular matrix Follicle-stimulating hormone Immunofluorescence Joint diseases Medicine Medicine & Public Health Meniscus Menopause Metabolic Diseases Metabolism Original Article Orthopedics Osteoarthritis Post-menopause Protein kinase A Sox9 protein |
title | FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway |
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