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2016 ; 1376
(1
): 53-64
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Systemic neutralization of TGF-? attenuates osteoarthritis
#MMPMID26837060
Xie L
; Tintani F
; Wang X
; Li F
; Zhen G
; Qiu T
; Wan M
; Crane J
; Chen Q
; Cao X
Ann N Y Acad Sci
2016[Jul]; 1376
(1
): 53-64
PMID26837060
show ga
Osteoarthritis (OA) is a major source of pain and disability worldwide with no
effective medical therapy due to poor understanding of its pathogenesis.
Transforming growth factor ? (TGF-?) has been reported to play a role in
subchondral bone pathology and articular cartilage degeneration during the
progression of OA. In this study, we demonstrated that systemic use of a
TGF-?-neutralizing antibody (1D11) attenuates OA progression by targeting
subchondral bone pathological features in rodent OA models. Systemic
administration of 1D11 preserves the subchondral bone microarchitecture,
preventing articular cartilage degeneration by inhibition of excessive TGF-?
activity, in both subchondral bone and the circulation. Moreover, the aberrant
increases in the numbers of blood vessels, nestin(+) mesenchymal stromal/stem
cells, and osterix(+) osteoblast progenitors were normalized by 1D11 systemic
injection. Thus, systemic neutralization of excessive TGF-? ligands effectively
prevented OA progression in animal models, with promising clinical implications
for OA treatment.
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