{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T22:26:57Z","timestamp":1794522417874,"version":"4.9.1"},"reference-count":53,"publisher":"BMJ","issue":"22","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Br J Sports Med"],"accepted":{"date-parts":[[2014,3,3]]},"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Glucocorticoid injection (GCI) and surgical rotator cuff repair are two widely used treatments for rotator cuff tendinopathy. Little is known about the way in which medical and surgical treatments affect the human rotator cuff tendon in vivo. We assessed the histological and immunohistochemical effects of these common treatments on the rotator cuff tendon.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study design<\/jats:title>\n                  <jats:p>Controlled laboratory study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Supraspinatus tendon biopsies were taken before and after treatment from 12 patients undergoing GCI and 8 patients undergoing surgical rotator cuff repair. All patients were symptomatic and none of the patients undergoing local GCI had full thickness tears of the rotator cuff. The tendon tissue was then analysed using histological techniques and immunohistochemistry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>There was a significant increase in nuclei count and vascularity after rotator cuff repair and not after GCI (both p=0.008). Hypoxia inducible factor 1\u03b1 (HIF-1\u03b1) and cell proliferation were only increased after rotator cuff repair (both p=0.03) and not GCI. The ionotropic <jats:italic>N<\/jats:italic>-methyl-<jats:sc>d<\/jats:sc>-aspartate receptor 1 (NMDAR1) glutamate receptor was only increased after GCI and not rotator cuff repair (p=0.016). An increase in glutamate was seen in both groups following treatment (both p=0.04), while an increase in the receptor metabotropic glutamate receptor 7 (mGluR7) was only seen after rotator cuff repair (p=0.016).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The increases in cell proliferation, vascularity and HIF-1\u03b1 after surgical rotator cuff repair appear consistent with a proliferative healing response, and these features are not seen after GCI. The increase in the glutamate receptor NMDAR1 after GCI raises concerns about the potential excitotoxic tendon damage that may result from this common treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bjsports-2013-093178","type":"journal-article","created":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T05:18:30Z","timestamp":1395983910000},"page":"1620-1626","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":84,"title":["Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy?"],"prefix":"10.1136","volume":"48","author":[{"given":"Benjamin John Floyd","family":"Dean","sequence":"first","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Louise","family":"Franklin","sequence":"additional","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Murphy","sequence":"additional","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad K","family":"Javaid","sequence":"additional","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Jonathan","family":"Carr","sequence":"additional","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2014,3,27]]},"reference":[{"key":"2025080112491062000_48.22.1620.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.25"},{"key":"2025080112491062000_48.22.1620.2","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.17.2000115"},{"key":"2025080112491062000_48.22.1620.3","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-013-3010-y"},{"key":"2025080112491062000_48.22.1620.4","unstructured":"Authority NBS. Electronic Prescribing & Financial Information for Practices (ePFIP). http:\/\/wwwnhsbsanhsuk\/PrescriptionServices\/963aspx , 2009."},{"key":"2025080112491062000_48.22.1620.5","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00386.2006"},{"key":"2025080112491062000_48.22.1620.6","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/0022-4804(77)90201-3","article-title":"Enzymatic changes in the healing rat Achilles tendon","volume":"23","author":"Stromberg","year":"1977","journal-title":"J Surg Rre"},{"key":"2025080112491062000_48.22.1620.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0838.2012.01475.x"},{"key":"2025080112491062000_48.22.1620.8","doi-asserted-by":"crossref","unstructured":"Post M Silver R Singh M . Rotator cuff tear. Diagnosis and treatment. Clin Orthop Relat Res 1983:78\u201391.","DOI":"10.1097\/00003086-198303000-00011"},{"key":"2025080112491062000_48.22.1620.9","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1302\/0301-620X.78B4.0780593","article-title":"Questionnaire on the perceptions of patients about shoulder surgery","volume":"78","author":"Dawson","year":"1996","journal-title":"J Bone Joint Surg Br Vol"},{"key":"2025080112491062000_48.22.1620.10","doi-asserted-by":"publisher","DOI":"10.1053\/j.oto.2013.05.003"},{"key":"2025080112491062000_48.22.1620.11","first-page":"291","article-title":"Quantification of histochemical staining by color deconvolution","volume":"23","author":"Ruifrok","year":"2001","journal-title":"Anal Quant Cytol Histol"},{"key":"2025080112491062000_48.22.1620.12","doi-asserted-by":"publisher","DOI":"10.1038\/83381"},{"key":"2025080112491062000_48.22.1620.13","doi-asserted-by":"publisher","DOI":"10.1177\/002215540305100503"},{"key":"2025080112491062000_48.22.1620.14","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-010-0210-6"},{"key":"2025080112491062000_48.22.1620.15","doi-asserted-by":"publisher","DOI":"10.1186\/1746-1596-7-42"},{"key":"2025080112491062000_48.22.1620.16","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.50.10.801"},{"key":"2025080112491062000_48.22.1620.17","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.129"},{"key":"2025080112491062000_48.22.1620.18","doi-asserted-by":"crossref","unstructured":"Buchbinder R Green S Youd JM . Corticosteroid injections for shoulder pain. Cochrane Database Syst Rev 2003(1):CD004016.","DOI":"10.1002\/14651858.CD004016"},{"key":"2025080112491062000_48.22.1620.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61160-9"},{"key":"2025080112491062000_48.22.1620.20","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.06.00125404"},{"key":"2025080112491062000_48.22.1620.21","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1020"},{"key":"2025080112491062000_48.22.1620.22","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.semarthrit.2013.08.006","article-title":"The risks and benefits of glucocorticoid treatment for tendinopathy: a systematic review of the effects of local glucocorticoid on tendon","volume":"43","author":"Dean","year":"2013","journal-title":"Semin Arthritis Rheum"},{"key":"2025080112491062000_48.22.1620.23","first-page":"259","article-title":"The response of human tendon to hydrocortisone injection","volume":"16","author":"Lee","year":"1975","journal-title":"Singapore Med J"},{"key":"2025080112491062000_48.22.1620.24","doi-asserted-by":"crossref","unstructured":"Poulsen RC Watts AC Murphy RJ . Glucocorticoids induce senescence in primary human tenocytes by inhibition of sirtuin 1 and activation of the p53\/p21 pathway: in vivo and in vitro evidence. Ann Rheum Dis 2013.","DOI":"10.1136\/annrheumdis-2012-203146"},{"key":"2025080112491062000_48.22.1620.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.10.093"},{"key":"2025080112491062000_48.22.1620.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2008.03.022"},{"key":"2025080112491062000_48.22.1620.27","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91622-5"},{"key":"2025080112491062000_48.22.1620.28","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2010.60"},{"key":"2025080112491062000_48.22.1620.29","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6451"},{"key":"2025080112491062000_48.22.1620.30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00411.2005"},{"key":"2025080112491062000_48.22.1620.31","doi-asserted-by":"crossref","first-page":"9821","DOI":"10.1523\/JNEUROSCI.19-22-09821.1999","article-title":"Protection from oxidative stress-induced apoptosis in cortical neuronal cultures by iron chelators is associated with enhanced DNA binding of hypoxia-inducible factor-1 and ATF-1\/CREB and increased expression of glycolytic enzymes, p21(waf1\/cip1), and erythropoietin","volume":"19","author":"Zaman","year":"1999","journal-title":"J Neurosci"},{"key":"2025080112491062000_48.22.1620.32","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1003"},{"key":"2025080112491062000_48.22.1620.33","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480230915"},{"key":"2025080112491062000_48.22.1620.34","doi-asserted-by":"publisher","DOI":"10.1385\/MN:24:1-3:107"},{"key":"2025080112491062000_48.22.1620.35","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s00167-003-0360-0","article-title":"Intratendinous glutamate levels and eccentric training in chronic Achilles tendinosis: a prospective study using microdialysis technique","volume":"11","author":"Alfredson","year":"2003","journal-title":"Knee Surg Sports Traumatol Arthrosc"},{"key":"2025080112491062000_48.22.1620.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.09.017"},{"key":"2025080112491062000_48.22.1620.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2004.11.004"},{"key":"2025080112491062000_48.22.1620.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2006.10.008"},{"key":"2025080112491062000_48.22.1620.39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-165"},{"key":"2025080112491062000_48.22.1620.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.csm.2012.07.001"},{"key":"2025080112491062000_48.22.1620.41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14023834"},{"key":"2025080112491062000_48.22.1620.42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042357"},{"key":"2025080112491062000_48.22.1620.43","doi-asserted-by":"publisher","DOI":"10.1177\/0363546511406395"},{"key":"2025080112491062000_48.22.1620.44","doi-asserted-by":"publisher","DOI":"10.4103\/0973-6042.94304"},{"key":"2025080112491062000_48.22.1620.45","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-012-2494-1"},{"key":"2025080112491062000_48.22.1620.46","first-page":"181","article-title":"Biology of tendon injury: healing, modeling and remodeling","volume":"6","author":"Sharma","year":"2006","journal-title":"J Musculoskelet Neuronal Interact"},{"key":"2025080112491062000_48.22.1620.47","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-0266(02)00207-3"},{"key":"2025080112491062000_48.22.1620.48","doi-asserted-by":"publisher","DOI":"10.1679\/aohc.63.17"},{"key":"2025080112491062000_48.22.1620.49","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPRJP39MIDSGBH"},{"key":"2025080112491062000_48.22.1620.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.11.070"},{"key":"2025080112491062000_48.22.1620.51","first-page":"839","article-title":"Unexpected presence of the neurotrophins NGF and BDNF and the neurotrophin receptor p75 in the tendon cells of the human Achilles tendon","volume":"24","author":"Bagge","year":"2009","journal-title":"Histol Histopathol"},{"key":"2025080112491062000_48.22.1620.52","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4804(76)90108-6"},{"key":"2025080112491062000_48.22.1620.53","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(78)90061-2"}],"container-title":["British Journal of Sports Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bjsports-2013-093178","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T19:49:20Z","timestamp":1754077760000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjsm.bmj.com\/lookup\/doi\/10.1136\/bjsports-2013-093178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,27]]},"references-count":53,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2014,11,10]]},"published-print":{"date-parts":[[2014,12]]}},"alternative-id":["10.1136\/bjsports-2013-093178"],"URL":"https:\/\/doi.org\/10.1136\/bjsports-2013-093178","relation":{},"ISSN":["0306-3674","1473-0480"],"issn-type":[{"value":"0306-3674","type":"print"},{"value":"1473-0480","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,27]]}}}