Parathyroid Hormone Inhibits Fatty Infiltration and Muscle Atrophy After Rotator Cuff Tear by Browning of Fibroadipogenic Progenitors in a Rodent Model
Background: Progressive fatty infiltration and muscle atrophy after rotator cuff tears lead to tendon repair failure and poor outcomes. Fibro-adipogenic progenitors (FAPs) are involved in fatty infiltration and muscle homeostasis of skeletal muscle. Inducing FAP differentiation into brown adipocyte–...
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| Veröffentlicht in: | The American journal of sports medicine 2023-10, Vol.51 (12), p.3251-3260 |
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| container_title | The American journal of sports medicine |
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| creator | Iio, Ryosuke Manaka, Tomoya Takada, Naoki Orita, Kumi Nakazawa, Katsumasa Hirakawa, Yoshihiro Ito, Yoichi Nakamura, Hiroaki |
| description | Background:
Progressive fatty infiltration and muscle atrophy after rotator cuff tears lead to tendon repair failure and poor outcomes. Fibro-adipogenic progenitors (FAPs) are involved in fatty infiltration and muscle homeostasis of skeletal muscle. Inducing FAP differentiation into brown adipocyte–like “beige adipocytes” suppresses fatty infiltration and muscle atrophy.
Hypothesis:
Parathyroid hormone (PTH) suppresses fatty infiltration and muscle atrophy after rotator cuff tears in a rat model by browning of FAPs.
Study Design:
Controlled laboratory study.
Methods:
PTH was administered subcutaneously for 4 or 8 weeks to a rotator cuff tear model in rats. After treatment, fatty infiltration of supraspinatus muscles was assessed using Oil Red O staining and muscle atrophy using wet muscle weight and muscle fiber cross-sectional area. Costaining of platelet-derived growth factor receptor α (FAP marker) and uncoupling protein 1 (browning marker) was performed to confirm FAP browning by PTH. Mouse-isolated FAPs were cultured with PTH and evaluated for browning-related gene expression and adipogenic differentiation using BODIPY staining. Myogenic differentiation of C2C12 myoblasts was evaluated using coculture of PTH-treated browning FAPs with C2C12.
Results:
PTH inhibited fatty infiltration after rotator cuff tear at 8 weeks. Rotator cuff wet muscle loss of PTH-treated rats was inhibited at 4 and 8 weeks. Furthermore, PTH-treated rats demonstrated larger myofiber cross-sectional area than did untreated rats at 4 and 8 weeks. Costaining indicated colocalization of platelet-derived growth factor receptor α and uncoupling protein 1 and promoted PTH-induced FAP browning. PTH increased the expression of browning-related genes in FAPs and suppressed fat droplet accumulation in vitro. Coculture with PTH-treated FAPs promoted C2C12 cell differentiation into myotubes.
Conclusion:
PTH induced FAP-derived beige adipocytes by upregulating browning-related gene expression, and the browning effect of PTH on FAPs inhibited fatty infiltration and muscle atrophy in the rat rotator cuff tear model. PTH might have potential as a therapeutic drug for fatty infiltration and muscle atrophy after rotator cuff tears.
Clinical Relevance:
PTH may expand treatment options for rotator cuff tears by reducing fatty infiltration and muscle atrophy after rotator cuff tears by browning of FAPs. |
| doi_str_mv | 10.1177/03635465231190389 |
| format | Article |
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Progressive fatty infiltration and muscle atrophy after rotator cuff tears lead to tendon repair failure and poor outcomes. Fibro-adipogenic progenitors (FAPs) are involved in fatty infiltration and muscle homeostasis of skeletal muscle. Inducing FAP differentiation into brown adipocyte–like “beige adipocytes” suppresses fatty infiltration and muscle atrophy.
Hypothesis:
Parathyroid hormone (PTH) suppresses fatty infiltration and muscle atrophy after rotator cuff tears in a rat model by browning of FAPs.
Study Design:
Controlled laboratory study.
Methods:
PTH was administered subcutaneously for 4 or 8 weeks to a rotator cuff tear model in rats. After treatment, fatty infiltration of supraspinatus muscles was assessed using Oil Red O staining and muscle atrophy using wet muscle weight and muscle fiber cross-sectional area. Costaining of platelet-derived growth factor receptor α (FAP marker) and uncoupling protein 1 (browning marker) was performed to confirm FAP browning by PTH. Mouse-isolated FAPs were cultured with PTH and evaluated for browning-related gene expression and adipogenic differentiation using BODIPY staining. Myogenic differentiation of C2C12 myoblasts was evaluated using coculture of PTH-treated browning FAPs with C2C12.
Results:
PTH inhibited fatty infiltration after rotator cuff tear at 8 weeks. Rotator cuff wet muscle loss of PTH-treated rats was inhibited at 4 and 8 weeks. Furthermore, PTH-treated rats demonstrated larger myofiber cross-sectional area than did untreated rats at 4 and 8 weeks. Costaining indicated colocalization of platelet-derived growth factor receptor α and uncoupling protein 1 and promoted PTH-induced FAP browning. PTH increased the expression of browning-related genes in FAPs and suppressed fat droplet accumulation in vitro. Coculture with PTH-treated FAPs promoted C2C12 cell differentiation into myotubes.
Conclusion:
PTH induced FAP-derived beige adipocytes by upregulating browning-related gene expression, and the browning effect of PTH on FAPs inhibited fatty infiltration and muscle atrophy in the rat rotator cuff tear model. PTH might have potential as a therapeutic drug for fatty infiltration and muscle atrophy after rotator cuff tears.
Clinical Relevance:
PTH may expand treatment options for rotator cuff tears by reducing fatty infiltration and muscle atrophy after rotator cuff tears by browning of FAPs.</description><identifier>ISSN: 0363-5465</identifier><identifier>EISSN: 1552-3365</identifier><identifier>DOI: 10.1177/03635465231190389</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Adipocytes ; Atrophy ; Gene expression ; Growth factors ; Rotator cuff ; Sports medicine</subject><ispartof>The American journal of sports medicine, 2023-10, Vol.51 (12), p.3251-3260</ispartof><rights>2023 The Author(s)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c260t-9199f7eb0f7cc3c52b5a9e0c1b9eb76b8ed540bf20b61f06cd5b911152c15c5b3</citedby><cites>FETCH-LOGICAL-c260t-9199f7eb0f7cc3c52b5a9e0c1b9eb76b8ed540bf20b61f06cd5b911152c15c5b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/03635465231190389$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/03635465231190389$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,777,781,21800,27905,27906,43602,43603</link.rule.ids></links><search><creatorcontrib>Iio, Ryosuke</creatorcontrib><creatorcontrib>Manaka, Tomoya</creatorcontrib><creatorcontrib>Takada, Naoki</creatorcontrib><creatorcontrib>Orita, Kumi</creatorcontrib><creatorcontrib>Nakazawa, Katsumasa</creatorcontrib><creatorcontrib>Hirakawa, Yoshihiro</creatorcontrib><creatorcontrib>Ito, Yoichi</creatorcontrib><creatorcontrib>Nakamura, Hiroaki</creatorcontrib><title>Parathyroid Hormone Inhibits Fatty Infiltration and Muscle Atrophy After Rotator Cuff Tear by Browning of Fibroadipogenic Progenitors in a Rodent Model</title><title>The American journal of sports medicine</title><addtitle>Am J Sports Med</addtitle><description>Background:
Progressive fatty infiltration and muscle atrophy after rotator cuff tears lead to tendon repair failure and poor outcomes. Fibro-adipogenic progenitors (FAPs) are involved in fatty infiltration and muscle homeostasis of skeletal muscle. Inducing FAP differentiation into brown adipocyte–like “beige adipocytes” suppresses fatty infiltration and muscle atrophy.
Hypothesis:
Parathyroid hormone (PTH) suppresses fatty infiltration and muscle atrophy after rotator cuff tears in a rat model by browning of FAPs.
Study Design:
Controlled laboratory study.
Methods:
PTH was administered subcutaneously for 4 or 8 weeks to a rotator cuff tear model in rats. After treatment, fatty infiltration of supraspinatus muscles was assessed using Oil Red O staining and muscle atrophy using wet muscle weight and muscle fiber cross-sectional area. Costaining of platelet-derived growth factor receptor α (FAP marker) and uncoupling protein 1 (browning marker) was performed to confirm FAP browning by PTH. Mouse-isolated FAPs were cultured with PTH and evaluated for browning-related gene expression and adipogenic differentiation using BODIPY staining. Myogenic differentiation of C2C12 myoblasts was evaluated using coculture of PTH-treated browning FAPs with C2C12.
Results:
PTH inhibited fatty infiltration after rotator cuff tear at 8 weeks. Rotator cuff wet muscle loss of PTH-treated rats was inhibited at 4 and 8 weeks. Furthermore, PTH-treated rats demonstrated larger myofiber cross-sectional area than did untreated rats at 4 and 8 weeks. Costaining indicated colocalization of platelet-derived growth factor receptor α and uncoupling protein 1 and promoted PTH-induced FAP browning. PTH increased the expression of browning-related genes in FAPs and suppressed fat droplet accumulation in vitro. Coculture with PTH-treated FAPs promoted C2C12 cell differentiation into myotubes.
Conclusion:
PTH induced FAP-derived beige adipocytes by upregulating browning-related gene expression, and the browning effect of PTH on FAPs inhibited fatty infiltration and muscle atrophy in the rat rotator cuff tear model. PTH might have potential as a therapeutic drug for fatty infiltration and muscle atrophy after rotator cuff tears.
Clinical Relevance:
PTH may expand treatment options for rotator cuff tears by reducing fatty infiltration and muscle atrophy after rotator cuff tears by browning of FAPs.</description><subject>Adipocytes</subject><subject>Atrophy</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Rotator cuff</subject><subject>Sports medicine</subject><issn>0363-5465</issn><issn>1552-3365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp1kVFLHDEUhUOx4Gr9Ab5d6EtfRpPJZjJ53C5dFZSK6POQZJLdyGyyTTLI_JL-3WZdQVD6dO7lfudw4SB0TvAFIZxfYtpQNm9YTQkRmLbiC5oRxuqK0oYdodn-Xu2BY3SS0jPGmPCmnaG_9zLKvJlicD1ch7gN3sCN3zjlcoKVzHkqq3VDLpgLHqTv4W5MejCwyDHsNhMsbDYRHkKWOURYjtbCo5ER1AQ_Y3jxzq8hWFg5FYPs3S6sjXca7uPrUDwJXAkuCb3xGe6KDN_QVyuHZM7e9BQ9rX49Lq-r299XN8vFbaXrBudKECEsNwpbrjXVrFZMCoM1UcIo3qjW9GyOla2xaojFje6ZEoQQVmvCNFP0FP045O5i-DOalLutS9oMg_QmjKmrW8bbOcaCF_T7B_Q5jNGX7wrFcSv4XNBCkQOlY0gpGtvtotvKOHUEd_uquk9VFc_FwZPk2ryn_t_wD_4HlVs</recordid><startdate>202310</startdate><enddate>202310</enddate><creator>Iio, Ryosuke</creator><creator>Manaka, Tomoya</creator><creator>Takada, Naoki</creator><creator>Orita, Kumi</creator><creator>Nakazawa, Katsumasa</creator><creator>Hirakawa, Yoshihiro</creator><creator>Ito, Yoichi</creator><creator>Nakamura, Hiroaki</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7TS</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>202310</creationdate><title>Parathyroid Hormone Inhibits Fatty Infiltration and Muscle Atrophy After Rotator Cuff Tear by Browning of Fibroadipogenic Progenitors in a Rodent Model</title><author>Iio, Ryosuke ; Manaka, Tomoya ; Takada, Naoki ; Orita, Kumi ; Nakazawa, Katsumasa ; Hirakawa, Yoshihiro ; Ito, Yoichi ; Nakamura, Hiroaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c260t-9199f7eb0f7cc3c52b5a9e0c1b9eb76b8ed540bf20b61f06cd5b911152c15c5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adipocytes</topic><topic>Atrophy</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Rotator cuff</topic><topic>Sports medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iio, Ryosuke</creatorcontrib><creatorcontrib>Manaka, Tomoya</creatorcontrib><creatorcontrib>Takada, Naoki</creatorcontrib><creatorcontrib>Orita, Kumi</creatorcontrib><creatorcontrib>Nakazawa, Katsumasa</creatorcontrib><creatorcontrib>Hirakawa, Yoshihiro</creatorcontrib><creatorcontrib>Ito, Yoichi</creatorcontrib><creatorcontrib>Nakamura, Hiroaki</creatorcontrib><collection>CrossRef</collection><collection>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of sports medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iio, Ryosuke</au><au>Manaka, Tomoya</au><au>Takada, Naoki</au><au>Orita, Kumi</au><au>Nakazawa, Katsumasa</au><au>Hirakawa, Yoshihiro</au><au>Ito, Yoichi</au><au>Nakamura, Hiroaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Parathyroid Hormone Inhibits Fatty Infiltration and Muscle Atrophy After Rotator Cuff Tear by Browning of Fibroadipogenic Progenitors in a Rodent Model</atitle><jtitle>The American journal of sports medicine</jtitle><addtitle>Am J Sports Med</addtitle><date>2023-10</date><risdate>2023</risdate><volume>51</volume><issue>12</issue><spage>3251</spage><epage>3260</epage><pages>3251-3260</pages><issn>0363-5465</issn><eissn>1552-3365</eissn><abstract>Background:
Progressive fatty infiltration and muscle atrophy after rotator cuff tears lead to tendon repair failure and poor outcomes. Fibro-adipogenic progenitors (FAPs) are involved in fatty infiltration and muscle homeostasis of skeletal muscle. Inducing FAP differentiation into brown adipocyte–like “beige adipocytes” suppresses fatty infiltration and muscle atrophy.
Hypothesis:
Parathyroid hormone (PTH) suppresses fatty infiltration and muscle atrophy after rotator cuff tears in a rat model by browning of FAPs.
Study Design:
Controlled laboratory study.
Methods:
PTH was administered subcutaneously for 4 or 8 weeks to a rotator cuff tear model in rats. After treatment, fatty infiltration of supraspinatus muscles was assessed using Oil Red O staining and muscle atrophy using wet muscle weight and muscle fiber cross-sectional area. Costaining of platelet-derived growth factor receptor α (FAP marker) and uncoupling protein 1 (browning marker) was performed to confirm FAP browning by PTH. Mouse-isolated FAPs were cultured with PTH and evaluated for browning-related gene expression and adipogenic differentiation using BODIPY staining. Myogenic differentiation of C2C12 myoblasts was evaluated using coculture of PTH-treated browning FAPs with C2C12.
Results:
PTH inhibited fatty infiltration after rotator cuff tear at 8 weeks. Rotator cuff wet muscle loss of PTH-treated rats was inhibited at 4 and 8 weeks. Furthermore, PTH-treated rats demonstrated larger myofiber cross-sectional area than did untreated rats at 4 and 8 weeks. Costaining indicated colocalization of platelet-derived growth factor receptor α and uncoupling protein 1 and promoted PTH-induced FAP browning. PTH increased the expression of browning-related genes in FAPs and suppressed fat droplet accumulation in vitro. Coculture with PTH-treated FAPs promoted C2C12 cell differentiation into myotubes.
Conclusion:
PTH induced FAP-derived beige adipocytes by upregulating browning-related gene expression, and the browning effect of PTH on FAPs inhibited fatty infiltration and muscle atrophy in the rat rotator cuff tear model. PTH might have potential as a therapeutic drug for fatty infiltration and muscle atrophy after rotator cuff tears.
Clinical Relevance:
PTH may expand treatment options for rotator cuff tears by reducing fatty infiltration and muscle atrophy after rotator cuff tears by browning of FAPs.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><doi>10.1177/03635465231190389</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0363-5465 |
| ispartof | The American journal of sports medicine, 2023-10, Vol.51 (12), p.3251-3260 |
| issn | 0363-5465 1552-3365 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2857840097 |
| source | SAGE Complete A-Z List; Alma/SFX Local Collection |
| subjects | Adipocytes Atrophy Gene expression Growth factors Rotator cuff Sports medicine |
| title | Parathyroid Hormone Inhibits Fatty Infiltration and Muscle Atrophy After Rotator Cuff Tear by Browning of Fibroadipogenic Progenitors in a Rodent Model |
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