{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:27:02Z","timestamp":1780586822663,"version":"3.54.1"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The etiology of spontaneous cranial cruciate ligament rupture in dogs is unknown despite being one of the most impacting orthopedic diseases in dogs. Numerous studies have contributed to the understanding of a multifactorial pathogenesis, this, however, without identifying a pivotal link to explain progressive collagen degeneration and osteoarthritic changes. In human medicine, recent reports have identified relaxin as a triggering factor in ligament ruptures in knee and metacarpal joints. We thus hypothesized that relaxin might also play a role in canine cruciate ligament rupture. Relaxin\u2019s primarily known property is connective tissue remodeling through collagenolysis. We therefore investigated relaxin and its cognate receptors LGR7\/LGR8 in 18 dogs with cranial cruciate ligament disease (CCLD) and compared them to a group of dogs with normal stifle joints. Applying immunohistochemistry (IHC), double immunofluorescence (dIF), and western blot analysis (WB), we found strong and significantly increased expression of both relaxin and its receptors in ruptured cruciate ligaments, and in synovial membranes. Pattern of immuno-staining on dIF strongly suggests relaxin binding to primed receptors and activation of signaling properties, which in turn may have affected collagen matrix metabolism. Thus, in canine cranial cruciate ligament disease, relaxin\/receptor signaling may be a primary trigger for collagen fiber degradation and collagen lysis, eventually followed by ligament rupture.<\/jats:p>","DOI":"10.3390\/ani12070819","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T12:20:25Z","timestamp":1648038025000},"page":"819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunoexpression of Relaxin and Its Receptors in Stifle Joints of Dogs with Cranial Cruciate Ligament Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Brunella","family":"Restucci","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariafrancesca","family":"Sgadari","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2578-7420","authenticated-orcid":false,"given":"Gerardo","family":"Fatone","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-6335","authenticated-orcid":false,"given":"Giovanni Della","family":"Valle","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8764-0101","authenticated-orcid":false,"given":"Federica","family":"Aragosa","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Caterino","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5837-7976","authenticated-orcid":false,"given":"Gianmarco","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-5013","authenticated-orcid":false,"given":"Gert W.","family":"Niebauer","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.5326\/0400385","article-title":"Cranial Cruciate Ligament Pathophysiology in Dogs with Cruciate Disease: A Review","volume":"40","author":"Hayashi","year":"2004","journal-title":"J. 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