{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:30:36Z","timestamp":1792611036497,"version":"4.5.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Osteoarthritis (OA) is a common joint disorder often affecting the knee. It is characterized by alterations of various joint tissues including subchondral bone and by chronic pain. Anti-nerve growth factor (NGF) antibodies have demonstrated improvement in pain associated with OA in phase 3 clinical trials but have not been approved due to an increased risk of developing rapidly progressive OA. The aim of this study was to investigate effects of systemic anti-NGF-treatment on structure and symptoms in rabbits with surgically induced joint instability.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This was elicited by anterior cruciate ligament transection and partial resection of the medial meniscus in right knee of 63 female rabbits, housed altogether in a 56\u00a0m<jats:sup>2<\/jats:sup> floor husbandry. Rabbits received either 0.1, 1 or 3\u00a0mg\/kg anti-NGF antibody intra-venously at weeks 1, 5 and 14 after surgery or vehicle. During in-life phase, static incapacitance tests were performed and joint diameter was measured. Following necropsy, gross morphological scoring and micro-computed tomography analysis of subchondral bone and cartilage were performed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> After surgery, rabbits unloaded operated joints, which was improved with 0.3 and 3\u00a0mg\/kg anti-NGF compared to vehicle injection during the first half of the study. The diameter of operated knee joints increased over contralateral measures. This increase was bigger in anti-NGF treated rabbits beginning 2\u00a0weeks after the first IV injection and became dose-dependent and more pronounced with time. In the 3\u00a0mg\/kg anti-NGF group, the bone volume fraction and trabecular thickness increased in the medio-femoral region of operated joints compared to contralateral and to vehicle-treated animals, while cartilage volume and to a lesser extent thickness decreased. Enlarged bony areas were found in right medio-femoral cartilage surfaces of animals receiving 1 and 3\u00a0mg\/kg anti-NGF. Alterations of all structural parameters were particularly distinct in a subgroup of three rabbits, which also exhibited more prominent symptomatic improvement.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study showed that anti-NGF administration exerted negative impact on structure in destabilized joints of rabbits, while pain-induced unloading of joints was improved. Our findings open up the possibility to better understand the effects of systemic anti-NGF, particularly on subchondral bone, and thus the occurrence of rapidly progressive OA in patients.<\/jats:p>","DOI":"10.3389\/fphys.2023.1201328","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T12:24:23Z","timestamp":1687782263000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Anti-NGF treatment worsens subchondral bone and cartilage measures while improving symptoms in floor-housed rabbits with osteoarthritis"],"prefix":"10.3389","volume":"14","author":[{"given":"Stephanie","family":"Menges","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Michaelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Kleinschmidt-D\u00f6rr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"B2","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.8434.1","volume-title":"Recent advances in understanding neurotrophin signaling","author":"Bothwell","year":"2016"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S498","DOI":"10.1016\/J.JOCA.2016.01.913","article-title":"Spontaneous home cage activity is sensitive to anti-NGF treatment or can be linked to joint stiffness in different models of surgery-induced osteoarthritis","volume":"24","author":"Brenneis","year":"2016","journal-title":"Osteoarthr. 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