Name	Diseases of the musculoskeletal system
ICD	ICD-11: FC0Z

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 knockdown enhanced Endoplasmic reticulum chaperone BiP (Grp78) expression through YTHDF2-mediated RNA degradation, which elicited ER stress, thereby promoting osteoblast apoptosis and inhibiting cell proliferation and differentiation under LPS-induced inflammatory condition.
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	METTL3 knockdown enhanced Endoplasmic reticulum chaperone BiP (Grp78) expression through YTHDF2-mediated RNA degradation, which elicited ER stress, thereby promoting osteoblast apoptosis and inhibiting cell proliferation and differentiation under LPS-induced inflammatory condition.
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	ALKBH5 promotes osteogenesis through modulating Runt-related transcription factor 2 (Runx2) mRNA stability.
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
	RNA degradation			hsa03018
Cell Process	RNA stability

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	Mettl3 knockdown not only reduced the expression of Vascular endothelial growth factor A (VEGFA) but also decreased the level of its splice variants, vegfa-164 and vegfa-188, in Mettl3-deficient BMSCs. These findings contribute to novel progress in understanding the role of epitranscriptomic regulation in the osteogenic differentiation of BMSCs.
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Alternative splicing
In-vitro Model	BMSCs (BMSCs were obtained from the femurs and tibias of 2-3-week-old Sprague-Dawley male rats (Animal Center of Sun Yat-sen University))

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	METTL3 acts on the m6A functional site of 1956 bp in hsa_circ_0008542. RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process.
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
	MC3T3-E1	Normal	Mus musculus	CVCL_0409
In-vivo Model	circ_0008542, where rats were injected with exosomes containing circ_0008542 into the tail vein for 8 weeks.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	METTL3 acts on the m6A functional site of 1956 bp in hsa_circ_0008542. RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process.
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Cell Process	RNA stability
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
	MC3T3-E1	Normal	Mus musculus	CVCL_0409
In-vivo Model	circ_0008542, where rats were injected with exosomes containing circ_0008542 into the tail vein for 8 weeks.

Ref 1	METTL3 mediates osteoblast apoptosis by regulating endoplasmic reticulum stress during LPS-induced inflammation. Cell Signal. 2022 Jul;95:110335. doi: 10.1016/j.cellsig.2022.110335. Epub 2022 Apr 21.
Ref 2	The RNA demethylase ALKBH5 promotes osteoblast differentiation by modulating Runx2 mRNA stability. FEBS Lett. 2021 Aug;595(15):2007-2014. doi: 10.1002/1873-3468.14145. Epub 2021 Jun 28.
Ref 3	Mettl3 Regulates Osteogenic Differentiation and Alternative Splicing of Vegfa in Bone Marrow Mesenchymal Stem Cells. Int J Mol Sci. 2019 Jan 28;20(3):551. doi: 10.3390/ijms20030551.
Ref 4	Circ_0008542 in osteoblast exosomes promotes osteoclast-induced bone resorption through m6A methylation. Cell Death Dis. 2021 Jun 18;12(7):628. doi: 10.1038/s41419-021-03915-1.