Postnatal deletion of Alk5 gene in meniscal cartilage accelerates age-dependent meniscal degeneration in mice
Wang,Quan1; Tan,Qiaoyan1; Xu,Wei1; Kuang,Liang1; Zhang,Bin1; Wang,Zuqiang1; Ni,Zhenhong1; Su,Nan1; Jin,Min1; Li,Can1; Jiang,Wanling1; Huang,Junlan1; Li,Fangfang1; Zhu,Ying1; Chen,Hangang1; Du,Xiaolan1; Chen,Di2; Deng,Chuxia3; Qi,Huabing1; Xie,Yangli1; Chen,Lin1
Source PublicationJournal of Cellular Physiology
AbstractActivation of transforming growth factor-β (TGF-β) signaling has been used to enhance healing of meniscal degeneration in several models. However, the exact role and molecular mechanism of TGF-β signaling in meniscus maintenance and degeneration are still not understood due to the absence of in vivo evidence. In this study, we found that the expression of activin receptor-like kinases 5 (ALK5) in the meniscus was decreased with the progression of age and/or osteoarthritis induced meniscal degeneration. Col2α1 positive cells were found to be specifically distributed in the superficial and inner zones of the anterior horn, as well as the inner zone of the posterior horn in mice, indicating that Col2α1-CreER mice can be a used for studying gene function in menisci. Furthermore, we deleted Alk5 in Col2α1 positive cells in meniscus by administering tamoxifen. Alterations in the menisci structure were evaluated histologically. The expression levels of genes and proteins associated with meniscus homeostasis and TGF-β signaling were analyzed by quantitative real-time PCR analysis (qRT-PCR) and immunohistochemistry (IHC). Our results revealed severe and progressive meniscal degeneration phenotype in 3- and 6-month-old Alk5 cKO mice compared with Cre-negative control, including aberrantly increased hypertrophic meniscal cells, severe fibrillation, and structure disruption of meniscus. qRT-PCR and IHC results showed that disruption of anabolic and catabolic homeostasis of chondrocytes may contribute to the meniscal degeneration phenotype observed in Alk5 cKO mice. Thus, TGF-β/ALK5 signaling plays a chondro-protective role in menisci homeostasis, in part, by inhibiting matrix degradation and maintaining extracellular matrix proteins levels in meniscal tissues.
Keywordactiving receptor-like kinases 5 (ALK5) matrix degradation meniscal degeneration transforming growth factor-β (TGF-β) signaling
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Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorChen,Lin
Affiliation1.Department of Rehabilitation Medicine,Center of Bone Metabolism and Repair,State Key Laboratory of Trauma,Burns and Combined Injury,Trauma Center,Research Institute of Surgery,Daping Hospital,Third Military Medical University,Chongqing,China
2.Department of Biochemistry,Rush University Medical Center,Chicago,United States
3.Faculty of Health Sciences,University of Macau,Macao
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Wang,Quan,Tan,Qiaoyan,Xu,Wei,et al. Postnatal deletion of Alk5 gene in meniscal cartilage accelerates age-dependent meniscal degeneration in mice[J]. Journal of Cellular Physiology,2018,234(1):595-605.
APA Wang,Quan.,Tan,Qiaoyan.,Xu,Wei.,Kuang,Liang.,Zhang,Bin.,Wang,Zuqiang.,Ni,Zhenhong.,Su,Nan.,Jin,Min.,Li,Can.,Jiang,Wanling.,Huang,Junlan.,Li,Fangfang.,Zhu,Ying.,Chen,Hangang.,Du,Xiaolan.,Chen,Di.,Deng,Chuxia.,Qi,Huabing.,...&Chen,Lin.(2018).Postnatal deletion of Alk5 gene in meniscal cartilage accelerates age-dependent meniscal degeneration in mice.Journal of Cellular Physiology,234(1),595-605.
MLA Wang,Quan,et al."Postnatal deletion of Alk5 gene in meniscal cartilage accelerates age-dependent meniscal degeneration in mice".Journal of Cellular Physiology 234.1(2018):595-605.
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