Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation

Hiroyuki Nakahara, Akihiko Hasegawa, Koji Otabe, Fumiaki Ayabe, Tetsuya Matsukawa, Naoko Onizuka, Yoshiaki Ito, Toshihumi Ozaki, Martin K. Lotz, Hiroshi Asahara

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2081-2089
Number of pages9
JournalArthritis and Rheumatism
Volume65
Issue number8
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Anterior Cruciate Ligament
Transcription Factors
Knee Osteoarthritis
Interleukin-1
Ligaments
Extracellular Matrix
Tissue Donors
Osteoarthritis
Small Interfering RNA
Knee
Immunohistochemistry
Chondrocytes
Knee Joint
Tendons
Cartilage
Autopsy
Joints
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Nakahara, H., Hasegawa, A., Otabe, K., Ayabe, F., Matsukawa, T., Onizuka, N., ... Asahara, H. (2013). Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation. Arthritis and Rheumatism, 65(8), 2081-2089. https://doi.org/10.1002/art.38020

Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation. / Nakahara, Hiroyuki; Hasegawa, Akihiko; Otabe, Koji; Ayabe, Fumiaki; Matsukawa, Tetsuya; Onizuka, Naoko; Ito, Yoshiaki; Ozaki, Toshihumi; Lotz, Martin K.; Asahara, Hiroshi.

In: Arthritis and Rheumatism, Vol. 65, No. 8, 08.2013, p. 2081-2089.

Research output: Contribution to journalArticle

Nakahara, H, Hasegawa, A, Otabe, K, Ayabe, F, Matsukawa, T, Onizuka, N, Ito, Y, Ozaki, T, Lotz, MK & Asahara, H 2013, 'Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation', Arthritis and Rheumatism, vol. 65, no. 8, pp. 2081-2089. https://doi.org/10.1002/art.38020
Nakahara H, Hasegawa A, Otabe K, Ayabe F, Matsukawa T, Onizuka N et al. Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation. Arthritis and Rheumatism. 2013 Aug;65(8):2081-2089. https://doi.org/10.1002/art.38020
Nakahara, Hiroyuki ; Hasegawa, Akihiko ; Otabe, Koji ; Ayabe, Fumiaki ; Matsukawa, Tetsuya ; Onizuka, Naoko ; Ito, Yoshiaki ; Ozaki, Toshihumi ; Lotz, Martin K. ; Asahara, Hiroshi. / Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation. In: Arthritis and Rheumatism. 2013 ; Vol. 65, No. 8. pp. 2081-2089.
@article{49c3c44eb2c84b5b887fe6b841fae70b,
title = "Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation",
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.",
author = "Hiroyuki Nakahara and Akihiko Hasegawa and Koji Otabe and Fumiaki Ayabe and Tetsuya Matsukawa and Naoko Onizuka and Yoshiaki Ito and Toshihumi Ozaki and Lotz, {Martin K.} and Hiroshi Asahara",
year = "2013",
month = "8",
doi = "10.1002/art.38020",
language = "English",
volume = "65",
pages = "2081--2089",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "8",

}

TY - JOUR

T1 - Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation

AU - Nakahara, Hiroyuki

AU - Hasegawa, Akihiko

AU - Otabe, Koji

AU - Ayabe, Fumiaki

AU - Matsukawa, Tetsuya

AU - Onizuka, Naoko

AU - Ito, Yoshiaki

AU - Ozaki, Toshihumi

AU - Lotz, Martin K.

AU - Asahara, Hiroshi

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84881335070&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881335070&partnerID=8YFLogxK

U2 - 10.1002/art.38020

DO - 10.1002/art.38020

M3 - Article

C2 - 23686683

AN - SCOPUS:84881335070

VL - 65

SP - 2081

EP - 2089

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 8

ER -