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Chemokine receptorâ 7 (CCR7) deficiency leads to delayed development of joint damage and functional deficits in a murine model of osteoarthritis

dc.contributor.authorSambamurthy, Nisha
dc.contributor.authorNguyen, Vu
dc.contributor.authorSmalley, Ryan
dc.contributor.authorXiao, Rui
dc.contributor.authorHankenson, Kurt
dc.contributor.authorGan, Justin
dc.contributor.authorMiller, Rachel E.
dc.contributor.authorMalfait, Anne‐marie
dc.contributor.authorDodge, George R.
dc.contributor.authorScanzello, Carla R.
dc.date.accessioned2018-05-15T20:14:48Z
dc.date.available2019-05-13T14:45:27Zen
dc.date.issued2018-03
dc.identifier.citationSambamurthy, Nisha; Nguyen, Vu; Smalley, Ryan; Xiao, Rui; Hankenson, Kurt; Gan, Justin; Miller, Rachel E.; Malfait, Anne‐marie ; Dodge, George R.; Scanzello, Carla R. (2018). "Chemokine receptorâ 7 (CCR7) deficiency leads to delayed development of joint damage and functional deficits in a murine model of osteoarthritis." Journal of Orthopaedic Research® 36(3): 864-875.
dc.identifier.issn0736-0266
dc.identifier.issn1554-527X
dc.identifier.urihttps://hdl.handle.net/2027.42/143717
dc.description.abstractElevated chemokine receptor Ccr7 is observed in knee osteoarthritis (OA) and associated with severity of symptoms. In this study, we confirmed that CCR7 protein expression is elevated in synovial tissue from OA patients by immunohistochemical staining. We then investigated whether Ccr7 deficiency impacted structural and functional joint degeneration utilizing a murine model of OA. OAâ like disease was induced in male C57BL/6 and Ccr7â deficient (Ccr7â /â ) mice by destabilization of the medial meniscus (DMM). Functional deficits were measured by computer integrated monitoring of spontaneous activity every 4 weeks after DMM surgery up 16 weeks. Joint degeneration was evaluated at 6 and 19 weeks postâ surgery by histopathology, and subchondral bone changes analyzed by microCT. Results showed reduction in locomotor activities in DMMâ operated C57BL/6 mice by 8 weeks, while activity decreases in Ccr7â /â mice were delayed until 16 weeks. Histopathologic evaluation showed minimal protection from early cartilage degeneration (pâ =â 0.06) and osteophytosis (pâ =â 0.04) in Ccr7â /â mice 6 weeks postâ DMM compared to C57BL/6 controls, but not at 19 weeks. However, subchondral bone mineral density (pâ =â 0.03) and histologic sclerosis (pâ =â 0.02) increased in response to surgery in C57BL/6 mice at 6 weeks, while Ccr7â /â mice were protected from these changes. Our results are the first to demonstrate a role for Ccr7 in early development of functional deficits and subchondral bone changes in the DMM model. Understanding the mechanism of Ccr7 receptor signaling in the initiation of joint pathology and disability will inform the development of innovative therapies to slow symptomatic OA development after injury. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res 36:864â 875, 2018.
dc.publisherWiley Periodicals, Inc.
dc.subject.othermurine behavioral analysis
dc.subject.otherosteoarthritis
dc.subject.otherchemokines
dc.subject.otheranimal model
dc.subject.otherbone remodeling
dc.titleChemokine receptorâ 7 (CCR7) deficiency leads to delayed development of joint damage and functional deficits in a murine model of osteoarthritis
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelKinesiology and Sports
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/143717/1/jor23671.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/143717/2/jor23671_am.pdf
dc.identifier.doi10.1002/jor.23671
dc.identifier.sourceJournal of Orthopaedic Research®
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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