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Transcription Factor Mohawk and the Pathogenesis of Human Anterior Cruciate Ligament Degradation Transcription Factor Mohawk and the Pathogenesis of Human Anterior Cruciate Ligament Degradation.
- Source :
-
Arthritis & Rheumatism . Aug2013, Vol. 65 Issue 8, p2081-2089. 9p. - Publication Year :
- 2013
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Abstract
- Objective To investigate the expression and function of Mohawk (MKX) in human adult anterior cruciate ligament (ACL) tissue and ligament cells from normal and osteoarthritis (OA)-affected knees. Methods Knee joints were obtained at autopsy (within 24-48 hours postmortem) from 13 donors with normal knees (mean ± SD age 36.9 ± 11.0 years), 16 donors with knee OA (age 79.7 ± 11.4 years), and 8 aging donors without knee OA (age 76.9 ± 12.9 years). All cartilage surfaces were graded macroscopically. MKX expression was analyzed by immunohistochemistry and quantitative polymerase chain reaction. ACL-derived cells were used to study regulation of MKX expression by interleukin-1β (IL-1β). MKX was knocked down with small interfering RNA (siRNA) to analyze the function of MKX in extracellular matrix (ECM) production and differentiation in ACL-derived cells. Results The expression of MKX was significantly decreased in ACL-derived cells from OA knees compared with normal knees. Consistent with this finding, immunohistochemistry analysis showed that MKX-positive cells were significantly reduced in ACL tissue from OA donors, in particular in cells located in disorientated fibers. In ACL-derived cells, IL-1β strongly suppressed MKX expression and reduced expression of the ligament ECM genes COL1A1 and TNXB. In contrast, SOX9, a chondrocyte master transcription factor, was up-regulated by IL-1β treatment. Importantly, knockdown of MKX expression with siRNA up-regulated SOX9 expression in ACL-derived cells, whereas the expression of COL1A1 and TNXB was reduced. Conclusion Reduced expression of MKX is a feature of degenerated ACL in OA-affected joints, and this may be mediated in part by IL-1β. MKX appears necessary to maintain the tissue-specific cellular differentiation status and ECM production in adult human tendons and ligaments. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00043591
- Volume :
- 65
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Arthritis & Rheumatism
- Publication Type :
- Academic Journal
- Accession number :
- 89398103
- Full Text :
- https://doi.org/10.1002/art.38020