{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T08:01:49Z","timestamp":1785571309764,"version":"3.56.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T00:00:00Z","timestamp":1568332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH AR 63144"],"award-info":[{"award-number":["NIH AR 63144"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The deposition of aggrecan\/hyaluronan (HA)\u2010rich matrix within the tendon body and surrounding peritenon impede tendon healing and result in compromised biomechanical properties. Hence, the development of novel strategies to achieve targeted removal of the aggrecan\u2010HA pericellular matrix may be effective in treating tendinopathy. The current study examined the therapeutic potential of a recombinant human hyaluronidase, rHuPH20 (FDA approved for reducing HA accumulation in tumors) for treating murine Achilles tendinopathy. The 12\u2010week\u2010old C57Bl\/6 male mice were injected with two doses of rHuTGF\u2010\u03b21 into the retrocalcaneal bursa (RCB) to induce a combined bursitis and tendinopathy. Twenty\u2010four hours following induction of injury, treatment groups were administered rHuPH20 Hyaluronidase (rHuPH20; Halozyme Therapeutics) into the RCB. At either 6\u2009h (acute), 9 days, or 25 days following hyaluronidase treatment, Achilles tendons were analyzed for gene expression, histology and immunohistochemistry, fluorophore\u2010assisted carbohydrate electrophoresis, and biomechanical properties. The rHuPH20 treatment was effective, particularly at the acute and 9\u2010day time points, in (a) removing HA deposits from the Achilles tendon and surrounding tissues, (b) improving biomechanical properties of the healing tendon, and (c) eliciting targeted increases in expression of specific cell fate, extracellular matrix metabolism, and inflammatory genes. The potential of rHuPH20 to effectively clear the pro\u2010inflammatory, HA\u2010rich matrix within the RCB and tendon strongly supports the future refinement of injectable glycosidase preparations as potential treatments to protect or regenerate tendon tissue by reducing inflammation and scarring in the presence of bursitis or other inducers of damage such as mechanical overuse. \u00a9 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:59\u201369, 2020<\/jats:p>","DOI":"10.1002\/jor.24459","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T08:32:21Z","timestamp":1567499541000},"page":"59-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In\u2010Vivo Efficacy of Recombinant Human Hyaluronidase (rHuPH20) Injection for Accelerated Healing of Murine Retrocalcaneal Bursitis and Tendinopathy"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0909-5264","authenticated-orcid":false,"given":"Sabah N.","family":"Rezvani","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Mechanics Virginia Tech  Blacksburg Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinnan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology) Rush University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology) Rush University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Midura","sequence":"additional","affiliation":[{"name":"Lerner Research Institute The Cleveland Clinic Foundation  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valbona","family":"Cali","sequence":"additional","affiliation":[{"name":"Lerner Research Institute The Cleveland Clinic Foundation  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Sandy","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Rush University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Plaas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology) Rush University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-9146","authenticated-orcid":false,"given":"Vincent M.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Mechanics Virginia Tech  Blacksburg Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,13]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.47.11.910"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2006.00510.x"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.67.BJR-2016-0340.R1"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-201106000-00006"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200308000-00009"},{"key":"e_1_2_7_1_7_1","first-page":"049","article-title":"Oral ibuprofen interferes with cellular healing responses in a murine model of Achilles tendinopathy","volume":"4","author":"Bittermann A","year":"2018","journal-title":"J Musculoskelet Disord Treat"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2018.1439483"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.7547\/0980095"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2012.10.020"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23393"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199507000-00021"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22398"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2008.03.005"},{"key":"e_1_2_7_1_15_1","first-page":"1203","article-title":"Effective targeting of the tumor microenvironment for cancer therapy","volume":"32","author":"Jiang P","year":"2012","journal-title":"Anticancer Res"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2015.12.024"},{"key":"e_1_2_7_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2006.05.027"},{"key":"e_1_2_7_1_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2018.1551442"},{"key":"e_1_2_7_1_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303060"},{"key":"e_1_2_7_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21558"},{"key":"e_1_2_7_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24027"},{"key":"e_1_2_7_1_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/10.3.273"},{"key":"e_1_2_7_1_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2001.0439"},{"key":"e_1_2_7_1_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0760132"},{"key":"e_1_2_7_1_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3420223"},{"key":"e_1_2_7_1_26_1","first-page":"1017","article-title":"Therapeutic efficacy of microtube\u2010embedded chondroitinase ABC in a canine clinical model of spinal cord injury","volume":"141","author":"Hu HZ","year":"2018","journal-title":"J Neurol"},{"key":"e_1_2_7_1_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.208694"},{"key":"e_1_2_7_1_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27196-5"},{"key":"e_1_2_7_1_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867311320090005"},{"key":"e_1_2_7_1_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-014-2246-5"},{"key":"e_1_2_7_1_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25595"},{"key":"e_1_2_7_1_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088479"},{"key":"e_1_2_7_1_33_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20001858"},{"key":"e_1_2_7_1_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072421"},{"key":"e_1_2_7_1_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000001562"},{"key":"e_1_2_7_1_36_1","first-page":"85","article-title":"Treatment of lumbar intervertebral disc displacement with chondroitinase ABC\u2010\u2010experimental basis for clinical application","volume":"14","author":"Takahashi T","year":"2004","journal-title":"Clin Calcium"},{"key":"e_1_2_7_1_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2019.03.029"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.24459","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.24459","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.24459","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.24459","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T05:48:13Z","timestamp":1694238493000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.24459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,13]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/jor.24459"],"URL":"https:\/\/doi.org\/10.1002\/jor.24459","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,13]]},"assertion":[{"value":"2019-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}