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10.1002/jcp.28885

http://scihub22266oqcxt.onion/10.1002/jcp.28885
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31161622!ä!31161622

suck abstract from ncbi


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pmid31161622      J+Cell+Physiol 2019 ; 234 (12): 23190-23201
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  • High concentration magnesium inhibits extracellular matrix calcification and protects articular cartilage via Erk/autophagy pathway #MMPMID31161622
  • Yue J; Jin S; Gu S; Sun R; Liang Q
  • J Cell Physiol 2019[Dec]; 234 (12): 23190-23201 PMID31161622show ga
  • The significant cytopathological changes of osteoarthritis are chondrocyte hypertrophy, proteoglycan loss, extracellular matrix (ECM) calcification, and terminally, the replacement of cartilage by bone. Meanwhile, magnesium ion (Mg(2+) ), as the second most abundant divalent cation in the human body, has been proved to inhibit the ECM calcification of hBMSCs (human bone marrow stromal cells), hVSMCs (Human vascular smooth muscle cells), and TDSCs (tendon-derived stem cells) in vitro studies. The ATDC5 cell line, which holds chondrocyte characteristics, was used in this study as an in vitro subject. We found that Mg(2+) can efficiently suppress the ECM calcification and downregulate both hypertrophy and matrix metalloproteinase-related genes. Meanwhile, Mg(2+) inhibits the formation of autophagy by inhibiting Erk phosphorylation signaling and lowers the expression of LC3, and eventually effectively reduces the formation of ECM calcification in vitro. In this study, we also used destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) animal model to further confirm the protective effect of Mg(2+) on articular cartilage. Compared with the control group (saline-injected), continuous intra-articular magnesium chloride (MgCl(2) ) injection can significantly alleviate the severity of cartilage calcification in OA animal model. Immunofluorescence staining also revealed that saline-injected DMM group had a higher positive rate of LC3 expression in cartilage chondrocytes, compared with MgCl(2) -injected DMM group. In general, Mg(2+) can significantly downregulate the hypertrophic gene Runx2, MMP13, and Col10alpha1, upregulate the chondrogenic genes Sox9 and Col1alpha1, inhibit the Erk phosphorylation signaling, reduce the expression of autophagy protein LC3, and effectively inhibit the ECM calcification of ATDC5. In vivo study also proved that intra-articular injection of Mg(2+) protected knee cartilage by inhibiting the autophagy formation.
  • |Animals[MESH]
  • |Autophagy/drug effects/physiology[MESH]
  • |Calcinosis/metabolism/pathology[MESH]
  • |Cartilage, Articular/drug effects/*pathology[MESH]
  • |Cell Line[MESH]
  • |Extracellular Matrix/drug effects/metabolism/*pathology[MESH]
  • |Humans[MESH]
  • |MAP Kinase Signaling System/*drug effects/physiology[MESH]
  • |Magnesium/*metabolism/pharmacology[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]


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