Name	Osteoarthritis
ICD	ICD-11: FA05

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	METTL3 has a functional role in mediates osteoarthritis progression by regulating NF-Kappa-B signaling and ECM synthesis in chondrocytes that shed insight on developing preventive and curative strategies for OA by focusing on METTL3 and mRNA methylation. Silencing of METTL3 promotes degradation of extracellular matrix (ECM) by reducing the expression of Collagenase 3 (MMP13) and Coll X, elevating the expression of Aggrecan and Coll II.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Inflammatory response and apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	The right knee joint of each OA mouse was injected with 1U of type VII collagenase over two consecutive days to obtain experimental OA joint, and the control mice received the equal volume of physiological saline.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	METTL3 is involved in OA probably by regulating the inflammatory response. METTL3 overexpression affects extracellular matrix degradation in OA by adjusting the balance between TIMPs and Collagenase 3 (MMP13).
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Inflammatory response
In-vitro Model	SW1353	Primary central chondrosarcoma	Homo sapiens	CVCL_0543

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 is involved in OA probably by regulating the inflammatory response. METTL3 overexpression affects extracellular matrix degradation in OA by adjusting the balance between TIMPs and Interstitial collagenase (MMP1).
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Inflammatory response
In-vitro Model	SW1353	Primary central chondrosarcoma	Homo sapiens	CVCL_0543

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 is involved in OA probably by regulating the inflammatory response. METTL3 overexpression affects extracellular matrix degradation in OA by adjusting the balance between Metalloproteinase inhibitor 1 (TIMP-1) and MMPs.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Inflammatory response
In-vitro Model	SW1353	Primary central chondrosarcoma	Homo sapiens	CVCL_0543

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 is involved in OA probably by regulating the inflammatory response. METTL3 overexpression affects extracellular matrix degradation in OA by adjusting the balance between Metalloproteinase inhibitor 2 (TIMP2) and MMPs.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Inflammatory response
In-vitro Model	SW1353	Primary central chondrosarcoma	Homo sapiens	CVCL_0543

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	m6A-mediated LINC00680 regulates the proliferation and ECM degradation of chondrocytes through LINC00680/m6A/NAD-dependent protein deacetylase sirtuin-1 (SIRT1) mRNA axis. METTL3-mediated LINC00680 accelerates osteoarthritis(OA) progression, which provides novel understanding of the role of m6A and lncRNA in OA.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	Chondrocytes (Chondrocytes were isolated from human cartilage and cultured)

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	METTL3 has a functional role in mediates osteoarthritis progression by regulating NF-Kappa-B signaling and ECM synthesis in chondrocytes that shed insight on developing preventive and curative strategies for OA by focusing on METTL3 and mRNA methylation. Silencing of METTL3 promotes degradation of extracellular matrix (ECM) by reducing the expression of MMP-13 and Prostaglandin G/H synthase 2 (Coll X/PTGS2), elevating the expression of Aggrecan and Coll II.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Inflammatory response and apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	The right knee joint of each OA mouse was injected with 1U of type VII collagenase over two consecutive days to obtain experimental OA joint, and the control mice received the equal volume of physiological saline.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	In osteoarthritis METTL3-mediated m6A modification decreased the expression of Thioredoxin (TXN/SASP), an E-1 enzyme crucial for the formation of autophagosomes, by attenuating its RNA stability. Silencing METTL3 enhanced autophagic flux and inhibited SASP expression in OA-FLS.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular senescence
	Cell autophagy
In-vitro Model	C-28/I2	Normal	Homo sapiens	CVCL_0187
	FLS (Rat fibroblast synovial cell line)
In-vivo Model	Mice were anaesthetized with isoflurane supplied in a mouse anaesthesia apparatus, followed with joint surgery on the right joint by sectioning the medial meniscotibial ligament.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	In osteoarthritis METTL3-mediated m6A modification decreased the expression of autophagy-related 7, an E-1 enzyme crucial for the formation of autophagosomes, by attenuating its RNA stability. Silencing METTL3 enhanced autophagic flux and inhibited Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) expression in OA-FLS.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular senescence
	Cell autophagy
In-vitro Model	C-28/I2	Normal	Homo sapiens	CVCL_0187
	FLS (Rat fibroblast synovial cell line)
In-vivo Model	Mice were anaesthetized with isoflurane supplied in a mouse anaesthesia apparatus, followed with joint surgery on the right joint by sectioning the medial meniscotibial ligament.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	m6A-mediated Long intergenic non-protein coding RNA 680 (LINC00680) regulates the proliferation and ECM degradation of chondrocytes through LINC00680/m6A/SIRT1 mRNA axis. METTL3-mediated LINC00680 accelerates osteoarthritis(OA) progression, which provides novel understanding of the role of m6A and lncRNA in OA.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	Chondrocytes (Chondrocytes were isolated from human cartilage and cultured)

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	FTO-mediated N6-methyladenosine demethylation downregulated AC008440.5 (AC008) transcription, while lower FTO expression led to upregulation of AC008 transcription in OA.
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	Chondrocytes (Chondrocytes were isolated from human cartilage and cultured)

Ref 1	METTL3 promotes experimental osteoarthritis development by regulating inflammatory response and apoptosis in chondrocyte. Biochem Biophys Res Commun. 2019 Aug 13;516(1):22-27. doi: 10.1016/j.bbrc.2019.05.168. Epub 2019 Jun 8.
Ref 2	METTL3 involves the progression of osteoarthritis probably by affecting ECM degradation and regulating the inflammatory response. Life Sci. 2021 Aug 1;278:119528. doi: 10.1016/j.lfs.2021.119528. Epub 2021 Apr 21.
Ref 3	N(6)-methyladenosine (m(6)A) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through m(6)A/SIRT1 manner. Cell Death Discov. 2022 May 2;8(1):240. doi: 10.1038/s41420-022-00890-0.
Ref 4	METTL3-mediated m(6)A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression. Ann Rheum Dis. 2022 Jan;81(1):87-99. doi: 10.1136/annrheumdis-2021-221091. Epub 2021 Oct 27.
Ref 5	m(6)A-mediated upregulation of AC008 promotes osteoarthritis progression through the miR-328-3p?AQP1/ANKH axis. Exp Mol Med. 2021 Nov;53(11):1723-1734. doi: 10.1038/s12276-021-00696-7. Epub 2021 Nov 4.