General Information of the Disease (ID: M6ADIS0113)
Name
Ossification of spinal ligaments
ICD
ICD-11: FA83
Full List of Target Gene(s) of This m6A-centered Disease Response
Bone morphogenetic protein 2 (BMP2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary The overexpression of ALKBH5 led to the activation of p-AKT, and Bone morphogenetic protein 2 (BMP2) was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.
Responsed Disease Ossification of spinal ligaments [ICD-11: FA83]
Responsed Drug MK22606 Investigative
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Ossification
In-vitro Model Ligamentum flavum cells (Ligamentum flavum cells)
RAC-alpha serine/threonine-protein kinase (AKT1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary The overexpression of ALKBH5 led to the activation of RAC-alpha serine/threonine-protein kinase (AKT1), and BMP2 was regulated by ALKBH5 through the AKT signaling pathway. ALKBH5 promoted the osteogenesis of the ligamentum flavum cells through BMP2 demethylation and AKT activation. MK22606 is an AKT inhibitor. Moreover, when ALKBH5 was knocked down in the ligamentum flavum cells, p-AKT was inhibited when compared with that in the overexpressed ALKBH5 and control groups.
Responsed Disease Ossification of spinal ligaments [ICD-11: FA83]
Responsed Drug MK22606 Investigative
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Ossification
In-vitro Model Ligamentum flavum cells (Ligamentum flavum cells)
X inactive specific transcript (XIST)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary METTL3 regulates ossification of the posterior longitudinal ligament via the lncRNA X inactive specific transcript (XIST)/miR-302a-3p/USP8 axis.
Responsed Disease Ossification of spinal ligaments [ICD-11: FA83]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Ubiquitination degradation
In-vitro Model Human primary ligament fibroblasts (Ligaments were dissected from a non-ossified site)
References
Ref 1 BMP2 Modified by the m(6)A Demethylation Enzyme ALKBH5 in the Ossification of the Ligamentum Flavum Through the AKT Signaling Pathway. Calcif Tissue Int. 2020 May;106(5):486-493. doi: 10.1007/s00223-019-00654-6. Epub 2020 Jan 2.
Ref 2 METTL3 Regulates Ossification of the Posterior Longitudinal Ligament via the lncRNA XIST/miR-302a-3p/USP8 Axis. Front Cell Dev Biol. 2021 Mar 5;9:629895. doi: 10.3389/fcell.2021.629895. eCollection 2021.