Name	Low bone mass disorder
ICD	ICD-11: FB83

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	loss of Fto also increased susceptibility of osteoblasts to genotoxic damage from metabolic stress induced by exposure to HF is also consistent with this model for FTO action. FTO functions intrinsically in osteoblasts through Heat shock 70 kDa protein 1A (HSPA1A)-NF-Kappa-B signaling to enhance the stability of mRNA of proteins that function to protect cells from genotoxic damage.
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	1H8 [Mouse hybridoma against human BMSC]	Normal	Mus musculus	CVCL_A7TU
In-vivo Model	FtoKO mice were backcrossed to WT C57BL/6 mice to remove Cre and bred to homozygosity. Results are reported for male mice on the same genetic background (C57BL6/J). For the diet-induced bone loss studies, mice were fed a 60% high-fat diet (D12492, Research Diets) from 6 wk of age to 24 wk. Genotyping strategies are available upon request. NBD (KKKKKKKKGGTALDWSWLQTE) with the Trp to Ala substitutions designed to render the peptide inactive underlined, was a gift from D.C.G. and dissolved in water before use. Next, 10 mg/kg NBD was intraperitoneally injected in 29-wk old FtoOc KO mice every other day for 9 d. One day after the last injection, bone was harvested for analysis of DNA damage.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	Knockout of Mettl3 reduces the translation efficiency of MSCs lineage allocator Parathyroid hormone 1 receptor (PTH1R), and disrupts the PTH-induced osteogenic and adipogenic responses in vivo.
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Parathyroid hormone synthesis, secretion and action			hsa04928
Cell Process	Adipogenesis
In-vivo Model	Mettl3fl/+ mice with C57BL6/J background were generated using CRISPR-Cas9 systems.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	Both depletion of FTO and application of the FTO inhibitor FB23 or FB23-2 impaired osteogenic differentiation of human MSCs. Knockdown of Peroxisome proliferator-activated receptor gamma (PPARG) promoted FTO-induced expression of the osteoblast biomarkers ALPL and OPN during osteogenic differentiation. This study demonstrates the functional significance of the FTO-PPARG axis in promoting the osteogenesis of human MSCs and sheds light on the role of m6A modification in mediating osteoporosis and osteonecrosis.
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Osteoclast differentiation			hsa04380
In-vitro Model	hMSCs (Human osteogenesis of mesenchymal stem cells (HUXMA-01001, Cyagen Biosciences, Suzhou, China))
In-vivo Model	Conditional knockout of Fto in bone in mice was generated as previously described. Throughout the study, mice were maintained on a 12 h: 12 h light:dark cycle in a specific pathogen-free facility.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runt-related transcription factor 2 (Runx2) mRNA and inhibiting osteogenic differentiation.
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
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-vivo Model	Female C57BL/6J mice (14 weeks old) were treated with bilateral ovariectomy under general anesthesia. Eight weeks after surgery, tibial plateau was harvested and the structure were evaluated with a SCANCO Medical uCT 40 scanner.

Ref 1	The RNA demethylase FTO is required for maintenance of bone mass and functions to protect osteoblasts from genotoxic damage. Proc Natl Acad Sci U S A. 2019 Sep 3;116(36):17980-17989. doi: 10.1073/pnas.1905489116. Epub 2019 Aug 21.
Ref 2	Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis. Nat Commun. 2018 Nov 14;9(1):4772. doi: 10.1038/s41467-018-06898-4.
Ref 3	The m(6)A demethylase FTO promotes the osteogenesis of mesenchymal stem cells by downregulating PPARG. Acta Pharmacol Sin. 2022 May;43(5):1311-1323. doi: 10.1038/s41401-021-00756-8. Epub 2021 Aug 30.
Ref 4	RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runx2 mRNA and inhibiting osteogenic differentiation. Aging (Albany NY). 2021 Sep 8;13(17):21134-21141. doi: 10.18632/aging.203377. Epub 2021 Sep 8.