Abstract
Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint destruction. A myriad of drugs targeting the immune abnormalities and downstream inflammatory cascades have been developed, but the joint destruction is not effectively halted. Here we report that aberrant activation of TGF-β in the subchondral bone marrow by immune response increases osteoprogenitors and uncoupled bone resorption and formation in RA mouse/rat models. Importantly, either systemic or local blockade of TGF-β activity in the subchondral bone attenuated articular cartilage degeneration in RA. Moreover, conditional deletion of TGF-β receptor II (Tgfbr2) in nestin-positive cells also effectively halted progression of RA joint destruction. Our data demonstrate that aberrant activation of TGF-β in the subchondral bone is involved at the onset of RA joint cartilage degeneration. Thus, modulation of subchondral bone TGF-β activity could be a potential therapy for RA joint destruction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2033-2043 |
| Number of pages | 11 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 30 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2015 |
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Keywords
- CARTILAGE DEGENERATION
- MESENCHYMAL STEM CELLS
- RHEUMATOID ARTHRITIS
- SUBCHONDRAL BONE
- TGF-β
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Aberrant Activation of TGF-β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joint Destruction. / Xu, Xin; Zheng, Liwei; Bian, Qin; Xie, Liang; Liu, Wenlong; Zhen, Gehua; Crane, Janet; Zhou, Xuedong; Cao, Xu.
In: Journal of Bone and Mineral Research, Vol. 30, No. 11, 01.11.2015, p. 2033-2043.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aberrant Activation of TGF-β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joint Destruction
AU - Xu, Xin
AU - Zheng, Liwei
AU - Bian, Qin
AU - Xie, Liang
AU - Liu, Wenlong
AU - Zhen, Gehua
AU - Crane, Janet
AU - Zhou, Xuedong
AU - Cao, Xu
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint destruction. A myriad of drugs targeting the immune abnormalities and downstream inflammatory cascades have been developed, but the joint destruction is not effectively halted. Here we report that aberrant activation of TGF-β in the subchondral bone marrow by immune response increases osteoprogenitors and uncoupled bone resorption and formation in RA mouse/rat models. Importantly, either systemic or local blockade of TGF-β activity in the subchondral bone attenuated articular cartilage degeneration in RA. Moreover, conditional deletion of TGF-β receptor II (Tgfbr2) in nestin-positive cells also effectively halted progression of RA joint destruction. Our data demonstrate that aberrant activation of TGF-β in the subchondral bone is involved at the onset of RA joint cartilage degeneration. Thus, modulation of subchondral bone TGF-β activity could be a potential therapy for RA joint destruction.
AB - Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint destruction. A myriad of drugs targeting the immune abnormalities and downstream inflammatory cascades have been developed, but the joint destruction is not effectively halted. Here we report that aberrant activation of TGF-β in the subchondral bone marrow by immune response increases osteoprogenitors and uncoupled bone resorption and formation in RA mouse/rat models. Importantly, either systemic or local blockade of TGF-β activity in the subchondral bone attenuated articular cartilage degeneration in RA. Moreover, conditional deletion of TGF-β receptor II (Tgfbr2) in nestin-positive cells also effectively halted progression of RA joint destruction. Our data demonstrate that aberrant activation of TGF-β in the subchondral bone is involved at the onset of RA joint cartilage degeneration. Thus, modulation of subchondral bone TGF-β activity could be a potential therapy for RA joint destruction.
KW - CARTILAGE DEGENERATION
KW - MESENCHYMAL STEM CELLS
KW - RHEUMATOID ARTHRITIS
KW - SUBCHONDRAL BONE
KW - TGF-β
UR - http://www.scopus.com/inward/record.url?scp=84945481472&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84945481472&partnerID=8YFLogxK
U2 - 10.1002/jbmr.2550
DO - 10.1002/jbmr.2550
M3 - Article
C2 - 25967237
AN - SCOPUS:84945481472
VL - 30
SP - 2033
EP - 2043
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 11
ER -