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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Pathol
2015 ; 185
(11
): 2875-85
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Attenuation of the progression of articular cartilage degeneration by inhibition
of TGF-?1 signaling in a mouse model of osteoarthritis
#MMPMID26355014
Chen R
; Mian M
; Fu M
; Zhao JY
; Yang L
; Li Y
; Xu L
Am J Pathol
2015[Nov]; 185
(11
): 2875-85
PMID26355014
show ga
Transforming growth factor beta 1 (TGF-?1) is implicated in osteoarthritis. We
therefore studied the role of TGF-?1 signaling in the development of
osteoarthritis in a developmental stage-dependent manner. Three different mouse
models were investigated. First, the Tgf-? receptor II (Tgfbr2) was specifically
removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to
12 months of age and were then euthanized for collection of knee and
temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to
destabilization of the medial meniscus (DMM) surgery. Knee joints were then
collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type
mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery,
these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then
euthanized for collection of knee joints. All joints were characterized for
evidences of articular cartilage degeneration. Initiation or acceleration of
articular cartilage degeneration was not observed by the genetic inactivation of
Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and
treatment with losartan both delayed the progression of articular cartilage
degeneration induced by DMM compared with control littermates. Therefore, we
conclude that inhibition of Tgf-?1 signaling protects adult knee joints in mice
against the development of osteoarthritis.