Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-β1 signaling in a mouse model of osteoarthritis.
Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β 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-β1 signaling protects adult knee joints in mice against the development of osteoarthritis.
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts.
Rebecca
R
Chen
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts.
Michelle
M
Mian
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts.
Martin
M
Fu
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts.
Jing Ying
JY
Zhao
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts.
Liang
L
Yang
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Faculty of Medicine, Harvard Medical School, Boston, Massachusetts. Electronic address: yefu_li@hms.harvard.edu.
Yefu
Y
Li
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Faculty of Medicine, Harvard Medical School, Boston, Massachusetts. Electronic address: lin_xu@hms.harvard.edu.
Lin
L
Xu
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D020219:Chondrogenesis / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007719:Knee Joint / Q000473:pathology; D019808:Losartan / Q000008:administration & dosage; D008592:Menisci, Tibial / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D019808:Losartan