Abstract
Osteoarthritis (OA) is the most common joint disease and typically begins with an aging-related disruption of the articular cartilage surface. Mechanisms leading to the aging-related cartilage surface degeneration remain to be determined. Here, we demonstrate that nonhistone chromatin protein high-mobility group box (HMGB) protein 2 is uniquely expressed in the superficial zone (SZ) of human articular cartilage. In human and murine cartilage, there is an aging-related loss of HMGB2 expression, ultimately leading to its complete absence. Mice genetically deficient in HMGB2 (Hmgb2-/-) show earlier onset of and more severe OA. This is associated with a profound reduction in cartilage cellularity attributable to increased cell death. These cellular changes precede glycosaminoglycan depletion and progressive cartilage erosions. Chondrocytes from Hmgb2-/- mice are more susceptible to apoptosis induction in vitro. In conclusion, HMGB2 is a transcriptional regulator specifically expressed in the SZ of human articular cartilage and supports chondrocyte survival. Aging is associated with a loss of HMGB2 expression and reduced cellularity, and this contributes to the development of OA.
| Original language | English |
|---|---|
| Pages (from-to) | 1181-1186 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 106 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jan 27 2009 |
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Keywords
- Apoptosis
- Chondrocytes
- HMGB
- Superficial zone
ASJC Scopus subject areas
- General
Cite this
Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis. / Taniguchi, Noboru; Caramés, Beatriz; Ronfani, Lorenza; Ulmer, Ulrich; Komiya, Setsuro; Bianchi, Marco E.; Lotz, Martin.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 4, 27.01.2009, p. 1181-1186.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis
AU - Taniguchi, Noboru
AU - Caramés, Beatriz
AU - Ronfani, Lorenza
AU - Ulmer, Ulrich
AU - Komiya, Setsuro
AU - Bianchi, Marco E.
AU - Lotz, Martin
PY - 2009/1/27
Y1 - 2009/1/27
N2 - Osteoarthritis (OA) is the most common joint disease and typically begins with an aging-related disruption of the articular cartilage surface. Mechanisms leading to the aging-related cartilage surface degeneration remain to be determined. Here, we demonstrate that nonhistone chromatin protein high-mobility group box (HMGB) protein 2 is uniquely expressed in the superficial zone (SZ) of human articular cartilage. In human and murine cartilage, there is an aging-related loss of HMGB2 expression, ultimately leading to its complete absence. Mice genetically deficient in HMGB2 (Hmgb2-/-) show earlier onset of and more severe OA. This is associated with a profound reduction in cartilage cellularity attributable to increased cell death. These cellular changes precede glycosaminoglycan depletion and progressive cartilage erosions. Chondrocytes from Hmgb2-/- mice are more susceptible to apoptosis induction in vitro. In conclusion, HMGB2 is a transcriptional regulator specifically expressed in the SZ of human articular cartilage and supports chondrocyte survival. Aging is associated with a loss of HMGB2 expression and reduced cellularity, and this contributes to the development of OA.
AB - Osteoarthritis (OA) is the most common joint disease and typically begins with an aging-related disruption of the articular cartilage surface. Mechanisms leading to the aging-related cartilage surface degeneration remain to be determined. Here, we demonstrate that nonhistone chromatin protein high-mobility group box (HMGB) protein 2 is uniquely expressed in the superficial zone (SZ) of human articular cartilage. In human and murine cartilage, there is an aging-related loss of HMGB2 expression, ultimately leading to its complete absence. Mice genetically deficient in HMGB2 (Hmgb2-/-) show earlier onset of and more severe OA. This is associated with a profound reduction in cartilage cellularity attributable to increased cell death. These cellular changes precede glycosaminoglycan depletion and progressive cartilage erosions. Chondrocytes from Hmgb2-/- mice are more susceptible to apoptosis induction in vitro. In conclusion, HMGB2 is a transcriptional regulator specifically expressed in the SZ of human articular cartilage and supports chondrocyte survival. Aging is associated with a loss of HMGB2 expression and reduced cellularity, and this contributes to the development of OA.
KW - Apoptosis
KW - Chondrocytes
KW - HMGB
KW - Superficial zone
UR - http://www.scopus.com/inward/record.url?scp=59049100910&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59049100910&partnerID=8YFLogxK
U2 - 10.1073/pnas.0806062106
DO - 10.1073/pnas.0806062106
M3 - Article
C2 - 19139395
AN - SCOPUS:59049100910
VL - 106
SP - 1181
EP - 1186
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 4
ER -