Abstract：
OBJECTIVE:Degeneration of articular cartilage leads to the development of osteoarthritis (OA), but the molecular pathology of the disease is poorly understood. The Disproportionate micromelia (Dmm) mouse has a deletion mutation in the C-propeptide encoding region of Col2a1, which leads to a defective cartilage matrix. The objective of this study was to determine whether heterozygous (Dmm/+) mice develop premature OA, and could therefore serve as an animal model for studying the molecular pathways leading to OA. DESIGN:Histological analysis was utilized to determine the state of articular cartilage degeneration in Dmm/+ mice at 3, 6, 9, 12, 15, and 22 months of age. Severity of OA was quantified with a modified Mankin scoring system. In addition, articular cartilage thickness, cell density, and the extracellular matrix (ECM) fraction of articular cartilage were quantified. RESULTS:Articular cartilage erosion was significantly more severe in Dmm/+ than in wild-type (+/+) mice beginning at 9 months, and modified Mankin scoring revealed Dmm/+ articular cartilage to be in a more severe osteoarthritic state as early as 3 months. In addition, Dmm/+ articular cartilage was thinner than +/+ cartilage and showed increased cell density and decreased matrix fraction compared with +/+ from the earliest time points measured. CONCLUSIONS:The present study demonstrates that Dmm/+ mice develop premature OA. The observed degenerative changes of Dmm/+ articular cartilage closely resemble those of human OA patients, with or without Col2a1 mutations, suggesting that Dmm/+ mice are a useful model for investigating mechanisms involved in OA.
journal_name
Osteoarthritis Cartilagejournal_title
Osteoarthritis and cartilageauthors
Bomsta BD,Bridgewater LC,Seegmiller REdoi
10.1016/j.joca.2005.11.011keywords:
subject
Has Abstractpub_date
2006-05-01 00:00:00pages
477-85issue
5eissn
1063-4584issn
1522-9653pii
S1063-4584(05)00325-0journal_volume
14pub_type
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journal_title：Osteoarthritis and cartilage
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
doi：10.1016/j.joca.2005.07.002
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journal_title：Osteoarthritis and cartilage
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doi：10.1016/j.joca.2008.01.004
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doi：10.1016/j.joca.2013.01.010
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pub_type： 杂志文章,多中心研究,随机对照试验
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doi：10.1016/j.joca.2004.02.005
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pub_type： 杂志文章
doi：10.1016/j.joca.2007.03.019
更新日期：2007-10-01 00:00:00
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
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更新日期：2013-12-01 00:00:00
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
doi：10.1016/j.joca.2005.11.014
更新日期：2006-05-01 00:00:00
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
doi：10.1016/s1063-4584(05)80055-x
更新日期：1995-09-01 00:00:00
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
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更新日期：2002-06-01 00:00:00
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pub_type： 杂志文章
doi：10.1053/joca.2002.0800
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
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更新日期：2006-10-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.joca.2015.12.008
更新日期：2016-06-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.joca.2014.12.002
更新日期：2015-03-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2011-04-01 00:00:00
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
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更新日期：2003-04-01 00:00:00
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pub_type： 杂志文章
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更新日期：2010-04-01 00:00:00
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章,meta分析,评审
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更新日期：2014-06-01 00:00:00
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
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更新日期：2016-05-01 00:00:00
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journal_title：Osteoarthritis and cartilage
pub_type： 杂志文章
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更新日期：2009-11-01 00:00:00
