Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling
Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Our previous studies showed that Yougui pills and Bushenhuoxue formula, both TCM prescriptions containing Corni Fructus (CF), have protecti...
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creator | Yu, Huan Yao, Sai Zhou, Chengchong Fu, Fangda Luo, Huan Du, Weibin Jin, Hongting Tong, Peijian Chen, Di Wu, Chengliang Ruan, Hongfeng |
description | Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Our previous studies showed that Yougui pills and Bushenhuoxue formula, both TCM prescriptions containing Corni Fructus (CF), have protective effects on osteoarthritis (OA). However, the underlying detailed components in both TCM prescriptions that play therapeutic roles have not been fully defined. Morroniside is a major iridoid glycoside and one of the quality control metrics of CF, but the effects of morroniside on OA remain largely elusive.
The study aims to assess the therapeutic effects of morroniside on cartilage degeneration using a mouse model of OA.
8-week-old male C57BL/6J mice were randomly divided into 4 groups: Sham, destabilization of the medial meniscus (DMM)-treated with vehicle, DMM-treated with low dose morroniside and DMM-treated with high dose morroniside. Histological staining, immunostaining, and TUNEL staining were conducted to detect changes in tissue morphology, expression of key molecules in chondrocytes, and chondrocyte apoptosis, respectively. Osteophyte formation, meniscus calcification, and subchondral sclerosis were quantitated using micro-CT. The expression of chondrocyte markers was also analyzed by Western blot in primary chondrocytes derived from mice treated with morroniside.
Morroniside attenuated the progression of OA in mice, resulting in substantially reduced osteophyte formation and subchondral sclerosis and lower OARSI scores. Specifically, morroniside significantly promoted cartilage matrix synthesis by increasing collagen type II expression and suppressing chondrocyte pyroptosis. Morroniside administration led to inhibition of matrix metalloproteinase-13 (MMP13), Caspase-1 and nod-like receptor protein-3 (NLRP3) expression in DMM mice and IL-1β-stimulated chondrocytes. In addition, morroniside attenuated the progression of OA by enhancing chondrocyte proliferation and inhibiting chondrocyte apoptosis. Morroniside also attenuated the progression of OA by inhibiting nuclear factor-κB (NF-κB) signaling.
Morroniside was protective against cartilage matrix degradation and reduced DMM-induced chondrocyte pyroptosis and apoptosis by the inhibition of NF-κB signaling.
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doi_str_mv | 10.1016/j.jep.2020.113447 |
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The study aims to assess the therapeutic effects of morroniside on cartilage degeneration using a mouse model of OA.
8-week-old male C57BL/6J mice were randomly divided into 4 groups: Sham, destabilization of the medial meniscus (DMM)-treated with vehicle, DMM-treated with low dose morroniside and DMM-treated with high dose morroniside. Histological staining, immunostaining, and TUNEL staining were conducted to detect changes in tissue morphology, expression of key molecules in chondrocytes, and chondrocyte apoptosis, respectively. Osteophyte formation, meniscus calcification, and subchondral sclerosis were quantitated using micro-CT. The expression of chondrocyte markers was also analyzed by Western blot in primary chondrocytes derived from mice treated with morroniside.
Morroniside attenuated the progression of OA in mice, resulting in substantially reduced osteophyte formation and subchondral sclerosis and lower OARSI scores. Specifically, morroniside significantly promoted cartilage matrix synthesis by increasing collagen type II expression and suppressing chondrocyte pyroptosis. Morroniside administration led to inhibition of matrix metalloproteinase-13 (MMP13), Caspase-1 and nod-like receptor protein-3 (NLRP3) expression in DMM mice and IL-1β-stimulated chondrocytes. In addition, morroniside attenuated the progression of OA by enhancing chondrocyte proliferation and inhibiting chondrocyte apoptosis. Morroniside also attenuated the progression of OA by inhibiting nuclear factor-κB (NF-κB) signaling.
Morroniside was protective against cartilage matrix degradation and reduced DMM-induced chondrocyte pyroptosis and apoptosis by the inhibition of NF-κB signaling.
[Display omitted]</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2020.113447</identifier><identifier>PMID: 33022338</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Animals ; Apoptosis - drug effects ; Arthritis, Experimental - pathology ; Arthritis, Experimental - prevention & control ; Cartilage degeneration ; Cartilage, Articular - drug effects ; Cartilage, Articular - pathology ; Chondrocytes - drug effects ; Disease Progression ; Glycosides - pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Morroniside ; NF-kappa B - metabolism ; NF-κB ; Osteoarthritis ; Osteoarthritis - pathology ; Osteoarthritis - prevention & control ; Pyroptosis ; Pyroptosis - drug effects ; Signal Transduction - drug effects</subject><ispartof>Journal of ethnopharmacology, 2021-02, Vol.266, p.113447-113447, Article 113447</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-34a8fd413481d85e5d31753bba4bbebecc747c8c0ff4fae3ce9fd566b3ce29513</citedby><cites>FETCH-LOGICAL-c353t-34a8fd413481d85e5d31753bba4bbebecc747c8c0ff4fae3ce9fd566b3ce29513</cites><orcidid>0000-0001-8868-9313</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jep.2020.113447$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33022338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Huan</creatorcontrib><creatorcontrib>Yao, Sai</creatorcontrib><creatorcontrib>Zhou, Chengchong</creatorcontrib><creatorcontrib>Fu, Fangda</creatorcontrib><creatorcontrib>Luo, Huan</creatorcontrib><creatorcontrib>Du, Weibin</creatorcontrib><creatorcontrib>Jin, Hongting</creatorcontrib><creatorcontrib>Tong, Peijian</creatorcontrib><creatorcontrib>Chen, Di</creatorcontrib><creatorcontrib>Wu, Chengliang</creatorcontrib><creatorcontrib>Ruan, Hongfeng</creatorcontrib><title>Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Our previous studies showed that Yougui pills and Bushenhuoxue formula, both TCM prescriptions containing Corni Fructus (CF), have protective effects on osteoarthritis (OA). However, the underlying detailed components in both TCM prescriptions that play therapeutic roles have not been fully defined. Morroniside is a major iridoid glycoside and one of the quality control metrics of CF, but the effects of morroniside on OA remain largely elusive.
The study aims to assess the therapeutic effects of morroniside on cartilage degeneration using a mouse model of OA.
8-week-old male C57BL/6J mice were randomly divided into 4 groups: Sham, destabilization of the medial meniscus (DMM)-treated with vehicle, DMM-treated with low dose morroniside and DMM-treated with high dose morroniside. Histological staining, immunostaining, and TUNEL staining were conducted to detect changes in tissue morphology, expression of key molecules in chondrocytes, and chondrocyte apoptosis, respectively. Osteophyte formation, meniscus calcification, and subchondral sclerosis were quantitated using micro-CT. The expression of chondrocyte markers was also analyzed by Western blot in primary chondrocytes derived from mice treated with morroniside.
Morroniside attenuated the progression of OA in mice, resulting in substantially reduced osteophyte formation and subchondral sclerosis and lower OARSI scores. Specifically, morroniside significantly promoted cartilage matrix synthesis by increasing collagen type II expression and suppressing chondrocyte pyroptosis. Morroniside administration led to inhibition of matrix metalloproteinase-13 (MMP13), Caspase-1 and nod-like receptor protein-3 (NLRP3) expression in DMM mice and IL-1β-stimulated chondrocytes. In addition, morroniside attenuated the progression of OA by enhancing chondrocyte proliferation and inhibiting chondrocyte apoptosis. Morroniside also attenuated the progression of OA by inhibiting nuclear factor-κB (NF-κB) signaling.
Morroniside was protective against cartilage matrix degradation and reduced DMM-induced chondrocyte pyroptosis and apoptosis by the inhibition of NF-κB signaling.
[Display omitted]</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Arthritis, Experimental - pathology</subject><subject>Arthritis, Experimental - prevention & control</subject><subject>Cartilage degeneration</subject><subject>Cartilage, Articular - drug effects</subject><subject>Cartilage, Articular - pathology</subject><subject>Chondrocytes - drug effects</subject><subject>Disease Progression</subject><subject>Glycosides - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Morroniside</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB</subject><subject>Osteoarthritis</subject><subject>Osteoarthritis - pathology</subject><subject>Osteoarthritis - prevention & control</subject><subject>Pyroptosis</subject><subject>Pyroptosis - drug effects</subject><subject>Signal Transduction - drug effects</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1OGzEUhS1EBWngAbqpvGQzqT32xDPqClBpK1HYwNryzx3iaMae2g5SHqGv1IfgmTAJsGTl-_OdI10fhL5QsqCELr-tF2uYFjWpS08Z5-IAzWgr6ko0gh2iGWGirVrB6TH6nNKaECIoJ0fomDFS14y1M_TvT4gxeJecBaxyBr9RGRJWU5hySK5U3uJpG9_a0GOzCt7GYLY7sKzVCIMLcScMKUNQMa-iy85gC48whGkEn7HeYudXTpeFf8A3V9XT_wuc3INXQxmcoE-9GhKcvr5zdH_14-7yV3V9-_P35fl1ZVjDcsW4anvLy7kttW0DjWVUNExrxbUGDcYILkxrSN_zXgEz0PW2WS51qequoWyOzva-Uwx_N5CyHF0yMAzKQ9gkWXPeUdF1pCko3aMmhpQi9HKKblRxKymRLwnItSwJyJcE5D6Bovn6ar_RI9h3xduXF-D7HoBy5KODKJNx4A1YF8FkaYP7wP4ZEG2cFA</recordid><startdate>20210210</startdate><enddate>20210210</enddate><creator>Yu, Huan</creator><creator>Yao, Sai</creator><creator>Zhou, Chengchong</creator><creator>Fu, Fangda</creator><creator>Luo, Huan</creator><creator>Du, Weibin</creator><creator>Jin, Hongting</creator><creator>Tong, Peijian</creator><creator>Chen, Di</creator><creator>Wu, Chengliang</creator><creator>Ruan, Hongfeng</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8868-9313</orcidid></search><sort><creationdate>20210210</creationdate><title>Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling</title><author>Yu, Huan ; Yao, Sai ; Zhou, Chengchong ; Fu, Fangda ; Luo, Huan ; Du, Weibin ; Jin, Hongting ; Tong, Peijian ; Chen, Di ; Wu, Chengliang ; Ruan, Hongfeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-34a8fd413481d85e5d31753bba4bbebecc747c8c0ff4fae3ce9fd566b3ce29513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Arthritis, Experimental - pathology</topic><topic>Arthritis, Experimental - prevention & control</topic><topic>Cartilage degeneration</topic><topic>Cartilage, Articular - drug effects</topic><topic>Cartilage, Articular - pathology</topic><topic>Chondrocytes - drug effects</topic><topic>Disease Progression</topic><topic>Glycosides - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Morroniside</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB</topic><topic>Osteoarthritis</topic><topic>Osteoarthritis - pathology</topic><topic>Osteoarthritis - prevention & control</topic><topic>Pyroptosis</topic><topic>Pyroptosis - drug effects</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Huan</creatorcontrib><creatorcontrib>Yao, Sai</creatorcontrib><creatorcontrib>Zhou, Chengchong</creatorcontrib><creatorcontrib>Fu, Fangda</creatorcontrib><creatorcontrib>Luo, Huan</creatorcontrib><creatorcontrib>Du, Weibin</creatorcontrib><creatorcontrib>Jin, Hongting</creatorcontrib><creatorcontrib>Tong, Peijian</creatorcontrib><creatorcontrib>Chen, Di</creatorcontrib><creatorcontrib>Wu, Chengliang</creatorcontrib><creatorcontrib>Ruan, Hongfeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Huan</au><au>Yao, Sai</au><au>Zhou, Chengchong</au><au>Fu, Fangda</au><au>Luo, Huan</au><au>Du, Weibin</au><au>Jin, Hongting</au><au>Tong, Peijian</au><au>Chen, Di</au><au>Wu, Chengliang</au><au>Ruan, Hongfeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2021-02-10</date><risdate>2021</risdate><volume>266</volume><spage>113447</spage><epage>113447</epage><pages>113447-113447</pages><artnum>113447</artnum><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Our previous studies showed that Yougui pills and Bushenhuoxue formula, both TCM prescriptions containing Corni Fructus (CF), have protective effects on osteoarthritis (OA). However, the underlying detailed components in both TCM prescriptions that play therapeutic roles have not been fully defined. Morroniside is a major iridoid glycoside and one of the quality control metrics of CF, but the effects of morroniside on OA remain largely elusive.
The study aims to assess the therapeutic effects of morroniside on cartilage degeneration using a mouse model of OA.
8-week-old male C57BL/6J mice were randomly divided into 4 groups: Sham, destabilization of the medial meniscus (DMM)-treated with vehicle, DMM-treated with low dose morroniside and DMM-treated with high dose morroniside. Histological staining, immunostaining, and TUNEL staining were conducted to detect changes in tissue morphology, expression of key molecules in chondrocytes, and chondrocyte apoptosis, respectively. Osteophyte formation, meniscus calcification, and subchondral sclerosis were quantitated using micro-CT. The expression of chondrocyte markers was also analyzed by Western blot in primary chondrocytes derived from mice treated with morroniside.
Morroniside attenuated the progression of OA in mice, resulting in substantially reduced osteophyte formation and subchondral sclerosis and lower OARSI scores. Specifically, morroniside significantly promoted cartilage matrix synthesis by increasing collagen type II expression and suppressing chondrocyte pyroptosis. Morroniside administration led to inhibition of matrix metalloproteinase-13 (MMP13), Caspase-1 and nod-like receptor protein-3 (NLRP3) expression in DMM mice and IL-1β-stimulated chondrocytes. In addition, morroniside attenuated the progression of OA by enhancing chondrocyte proliferation and inhibiting chondrocyte apoptosis. Morroniside also attenuated the progression of OA by inhibiting nuclear factor-κB (NF-κB) signaling.
Morroniside was protective against cartilage matrix degradation and reduced DMM-induced chondrocyte pyroptosis and apoptosis by the inhibition of NF-κB signaling.
[Display omitted]</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>33022338</pmid><doi>10.1016/j.jep.2020.113447</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-8868-9313</orcidid></addata></record> |
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subjects | Animals Apoptosis - drug effects Arthritis, Experimental - pathology Arthritis, Experimental - prevention & control Cartilage degeneration Cartilage, Articular - drug effects Cartilage, Articular - pathology Chondrocytes - drug effects Disease Progression Glycosides - pharmacology Male Mice Mice, Inbred C57BL Morroniside NF-kappa B - metabolism NF-κB Osteoarthritis Osteoarthritis - pathology Osteoarthritis - prevention & control Pyroptosis Pyroptosis - drug effects Signal Transduction - drug effects |
title | Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling |
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