Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs
Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert prote...
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| Veröffentlicht in: | International immunopharmacology 2017-02, Vol.43, p.236-242 |
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| creator | Zhu, Jun Tang, Haoyu Zhang, Zhenhua Zhang, Yong Qiu, Chengfeng Zhang, Ling Huang, Pinge Li, Feng |
| description | Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration.
[Display omitted]
•Kaempferol enhances the viability of BMSCs.•Kaempferol inhibits LPS-induced matrix degradation.•Kaempferol decreases LPS-induced lipid accumulation in BMSCs.•Kaempferol inhibits LPS-induced activation of the NF-κB in BMSCs. |
| doi_str_mv | 10.1016/j.intimp.2016.12.020 |
| format | Article |
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[Display omitted]
•Kaempferol enhances the viability of BMSCs.•Kaempferol inhibits LPS-induced matrix degradation.•Kaempferol decreases LPS-induced lipid accumulation in BMSCs.•Kaempferol inhibits LPS-induced activation of the NF-κB in BMSCs.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2016.12.020</identifier><identifier>PMID: 28043032</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adipogenesis ; Adipogenesis - drug effects ; Aggrecan ; Animals ; Apoptosis ; Apoptosis - drug effects ; Autografts ; Biocompatibility ; Biomedical materials ; BMSCs ; Bone marrow ; Bone Marrow Cells - drug effects ; Bone Marrow Cells - physiology ; Carnitine ; Carnitine O-Palmitoyltransferase - metabolism ; Catabolism ; Cell Differentiation - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Cells, Cultured ; Collagen (type II) ; Collagenase 3 ; Cytokines ; Cytokines - metabolism ; Cytotoxicity ; Degeneration ; Differentiation ; Enzymes ; Gene expression ; Genes ; Humans ; Inflammation ; Inflammation - drug therapy ; Inflammation Mediators - metabolism ; Interleukin 10 ; Intervertebral Disc Degeneration - drug therapy ; Intervertebral discs ; IVD degeneration ; Kaempferol ; Kaempferols - therapeutic use ; Lipid metabolism ; Lipopolysaccharides ; Lipopolysaccharides - immunology ; Matrix metalloproteinase ; Matrix Metalloproteinase 3 - metabolism ; Mesenchymal Stromal Cells - drug effects ; Mesenchymal Stromal Cells - physiology ; Mesenchyme ; Metalloproteinase ; Mitosis ; Nuclei (cytology) ; Osteogenesis ; Osteogenesis - drug effects ; Osteoporosis ; PPAR gamma - metabolism ; Rabbits ; Regeneration ; Socioeconomic factors ; SOX9 Transcription Factor - genetics ; SOX9 Transcription Factor - metabolism ; Spinal cord ; Staining ; Stem cells ; Toxicity ; Translocation</subject><ispartof>International immunopharmacology, 2017-02, Vol.43, p.236-242</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Feb 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-e9717346c95dd7bfafb3ce599b37561e0db3ba0a5c776da2d439b370c77a7f0e3</citedby><cites>FETCH-LOGICAL-c390t-e9717346c95dd7bfafb3ce599b37561e0db3ba0a5c776da2d439b370c77a7f0e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1567576916305215$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28043032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Jun</creatorcontrib><creatorcontrib>Tang, Haoyu</creatorcontrib><creatorcontrib>Zhang, Zhenhua</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><creatorcontrib>Qiu, Chengfeng</creatorcontrib><creatorcontrib>Zhang, Ling</creatorcontrib><creatorcontrib>Huang, Pinge</creatorcontrib><creatorcontrib>Li, Feng</creatorcontrib><title>Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration.
[Display omitted]
•Kaempferol enhances the viability of BMSCs.•Kaempferol inhibits LPS-induced matrix degradation.•Kaempferol decreases LPS-induced lipid accumulation in BMSCs.•Kaempferol inhibits LPS-induced activation of the NF-κB in BMSCs.</description><subject>Adipogenesis</subject><subject>Adipogenesis - drug effects</subject><subject>Aggrecan</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Autografts</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>BMSCs</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bone Marrow Cells - physiology</subject><subject>Carnitine</subject><subject>Carnitine O-Palmitoyltransferase - metabolism</subject><subject>Catabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Collagen (type II)</subject><subject>Collagenase 3</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Cytotoxicity</subject><subject>Degeneration</subject><subject>Differentiation</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation Mediators - metabolism</subject><subject>Interleukin 10</subject><subject>Intervertebral Disc Degeneration - drug therapy</subject><subject>Intervertebral discs</subject><subject>IVD degeneration</subject><subject>Kaempferol</subject><subject>Kaempferols - therapeutic use</subject><subject>Lipid metabolism</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - immunology</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 3 - metabolism</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Mesenchymal Stromal Cells - physiology</subject><subject>Mesenchyme</subject><subject>Metalloproteinase</subject><subject>Mitosis</subject><subject>Nuclei (cytology)</subject><subject>Osteogenesis</subject><subject>Osteogenesis - drug effects</subject><subject>Osteoporosis</subject><subject>PPAR gamma - metabolism</subject><subject>Rabbits</subject><subject>Regeneration</subject><subject>Socioeconomic factors</subject><subject>SOX9 Transcription Factor - genetics</subject><subject>SOX9 Transcription Factor - metabolism</subject><subject>Spinal cord</subject><subject>Staining</subject><subject>Stem cells</subject><subject>Toxicity</subject><subject>Translocation</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1TAQhiNERS_wBghZYsMmqR3HcbJBgiMKiFO1UmFt-TKpfBTbwU6KzmPwxjhKy4IFK3vG3_wznr8oXhNcEUzay0Nl_WzdVNU5qkhd4Ro_K85Ix7uScMye5ztrecl4258W5ykdMM75hrwoTusONxTT-qz4_U2CmwaIYURpDL8SyqoQHyDOoKIckbFJIwP34CHK2QaP1BG5YOxwtP4e7W_vSuvNosGgkGYIK5hsupTGTk8Bsk7JUXoNSHqTOwyjdG5Ti5Cm4BPkLPp4fbdLL4uTQY4JXj2eF8WPq0_fd1_K_c3nr7sP-1LTHs8l9Jxw2rS6Z8ZwNchBUQ2s7xXlrCWAjaJKYsk0562RtWno-oRzKPmAgV4U7zbdKYafC6RZuPxVGPOcEJYkSMcYbpvcJqNv_0EPYYk-TydIT0nbd7heqWajdAwpRRjEFK2T8SgIFqtl4iA2y8RqmSC1yJblsjeP4otyYP4WPXmUgfcbAHkbDxaiSNpCXqaxEfQsTLD_7_AHb8us5w</recordid><startdate>201702</startdate><enddate>201702</enddate><creator>Zhu, Jun</creator><creator>Tang, Haoyu</creator><creator>Zhang, Zhenhua</creator><creator>Zhang, Yong</creator><creator>Qiu, Chengfeng</creator><creator>Zhang, Ling</creator><creator>Huang, Pinge</creator><creator>Li, Feng</creator><general>Elsevier B.V</general><general>Elsevier BV</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>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201702</creationdate><title>Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs</title><author>Zhu, Jun ; Tang, Haoyu ; Zhang, Zhenhua ; Zhang, Yong ; Qiu, Chengfeng ; Zhang, Ling ; Huang, Pinge ; Li, Feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-e9717346c95dd7bfafb3ce599b37561e0db3ba0a5c776da2d439b370c77a7f0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adipogenesis</topic><topic>Adipogenesis - drug effects</topic><topic>Aggrecan</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Autografts</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>BMSCs</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Bone Marrow Cells - physiology</topic><topic>Carnitine</topic><topic>Carnitine O-Palmitoyltransferase - metabolism</topic><topic>Catabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Collagen (type II)</topic><topic>Collagenase 3</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Cytotoxicity</topic><topic>Degeneration</topic><topic>Differentiation</topic><topic>Enzymes</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation Mediators - metabolism</topic><topic>Interleukin 10</topic><topic>Intervertebral Disc Degeneration - drug therapy</topic><topic>Intervertebral discs</topic><topic>IVD degeneration</topic><topic>Kaempferol</topic><topic>Kaempferols - therapeutic use</topic><topic>Lipid metabolism</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - immunology</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 3 - metabolism</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Mesenchymal Stromal Cells - physiology</topic><topic>Mesenchyme</topic><topic>Metalloproteinase</topic><topic>Mitosis</topic><topic>Nuclei (cytology)</topic><topic>Osteogenesis</topic><topic>Osteogenesis - drug effects</topic><topic>Osteoporosis</topic><topic>PPAR gamma - metabolism</topic><topic>Rabbits</topic><topic>Regeneration</topic><topic>Socioeconomic factors</topic><topic>SOX9 Transcription Factor - genetics</topic><topic>SOX9 Transcription Factor - metabolism</topic><topic>Spinal cord</topic><topic>Staining</topic><topic>Stem cells</topic><topic>Toxicity</topic><topic>Translocation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Jun</creatorcontrib><creatorcontrib>Tang, Haoyu</creatorcontrib><creatorcontrib>Zhang, Zhenhua</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><creatorcontrib>Qiu, Chengfeng</creatorcontrib><creatorcontrib>Zhang, Ling</creatorcontrib><creatorcontrib>Huang, Pinge</creatorcontrib><creatorcontrib>Li, Feng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Jun</au><au>Tang, Haoyu</au><au>Zhang, Zhenhua</au><au>Zhang, Yong</au><au>Qiu, Chengfeng</au><au>Zhang, Ling</au><au>Huang, Pinge</au><au>Li, Feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2017-02</date><risdate>2017</risdate><volume>43</volume><spage>236</spage><epage>242</epage><pages>236-242</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration.
[Display omitted]
•Kaempferol enhances the viability of BMSCs.•Kaempferol inhibits LPS-induced matrix degradation.•Kaempferol decreases LPS-induced lipid accumulation in BMSCs.•Kaempferol inhibits LPS-induced activation of the NF-κB in BMSCs.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28043032</pmid><doi>10.1016/j.intimp.2016.12.020</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | International immunopharmacology, 2017-02, Vol.43, p.236-242 |
| issn | 1567-5769 1878-1705 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adipogenesis Adipogenesis - drug effects Aggrecan Animals Apoptosis Apoptosis - drug effects Autografts Biocompatibility Biomedical materials BMSCs Bone marrow Bone Marrow Cells - drug effects Bone Marrow Cells - physiology Carnitine Carnitine O-Palmitoyltransferase - metabolism Catabolism Cell Differentiation - drug effects Cell proliferation Cell Proliferation - drug effects Cells, Cultured Collagen (type II) Collagenase 3 Cytokines Cytokines - metabolism Cytotoxicity Degeneration Differentiation Enzymes Gene expression Genes Humans Inflammation Inflammation - drug therapy Inflammation Mediators - metabolism Interleukin 10 Intervertebral Disc Degeneration - drug therapy Intervertebral discs IVD degeneration Kaempferol Kaempferols - therapeutic use Lipid metabolism Lipopolysaccharides Lipopolysaccharides - immunology Matrix metalloproteinase Matrix Metalloproteinase 3 - metabolism Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - physiology Mesenchyme Metalloproteinase Mitosis Nuclei (cytology) Osteogenesis Osteogenesis - drug effects Osteoporosis PPAR gamma - metabolism Rabbits Regeneration Socioeconomic factors SOX9 Transcription Factor - genetics SOX9 Transcription Factor - metabolism Spinal cord Staining Stem cells Toxicity Translocation |
| title | Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs |
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