TABLE 2.

The role of m⁶A in musculoskeletal disorders.

Diseases	M6A component	Samples and condition	Function	Regulation	Target	Role in disease	References
OS	METTL14, METTL3, FTO, ALKBH5	MG63/DXR (doxorubicin treatment)	Oncogene	↓:METTL14/FTO; ↑:METTL3/ALKBH5	Wnt signaling	Emergence and maintaining of OSCs, promoting drug resistance	Wang Y. et al., 2019
	ALKBH5	70 pairs of OS and normal tissues Osteoblast cell line and OS cell lines	Oncogene	↑	PVT1	Promoting OS cell proliferation	Chen et al., 2020
	METTL3	HOS, SAOS-2, U2OS, and MG63 cells	Oncogene	↑	ATAD2	Enhancing OS cell growth and metastasis	Zhou et al., 2020
	METTL3	28 pairs of OS cancerous and paracancerous tissues; hFOB1.19 and OS cell lines	Oncogene	↑	DRG1	Promoting OS progression	Ling et al., 2020
	METTL3	40 paired of OS tissues and adjacent tissues Osteoblast cells and OS cell lines	Oncogene	↑	LEF1	Promoting OS progression	Miao et al., 2019
OA	METTL3	ATDC5 cells	promotor	↑	NF-κB signaling	Promoting inflammatory response, collagen synthesis and degradation, and cell apoptosis in chondrocytes	Liu Q. et al., 2019
RA	METTL3	47 RA patients and 30 health controls; THP-1 cell	promotor	↑	NF-κB signaling	Promoting RA disease activity	Wang J. et al., 2019
OP	METTL3	METTL3 knock-out and knock-in mice; primary MSCs	Suppressor	↓	PTH/Pth1r signaling	Impairing bone formation	Wu et al., 2018
	METTL3	Female OP patients and control subjects; METTL3+/– mice	Suppressor	↓	miR320/RUNX2	Promoting OP development	Yan et al., 2020
	FTO	44 female/male individuals with/without OP Young and aged C57BL/6J mice	promotor	↑	Pparg	Promoting the shift of osteoporotic BMSC fate to adipocyte	Shen et al., 2018
	FTO	FTOflx/flx (FTOf/f) mice	Suppressor	↑	ER stress pathway	Protecting osteoblasts from genotoxic damage Maintaining bone mass	Zhang Q. et al., 2019

↑, Upregulation; ↓, Downregulation; ALKBH5, alkB homolog 5, ATAD2, ATPase family AAA domain containing 2; DRG1, GTP-binding protein 1; ER, endoplasmic reticulum; FTO, fat mass and obesity-associated protein; LEF1, lymphoid enhancer binding factor 1; METTL3, methyltransferase-like 3; METTL14, methyltransferase-like 14; NF-κB, nuclear factor κB; OA, osteoarthritis; OP, osteoporosis; OS, osteosarcoma; Pparg, peroxisome proliferator-activated receptor γ; PTH/Pth1r, parathyroid hormone/parathyroid hormone receptor-1; PVT1, plasmacytoma variant translocation 1; RA, rheumatoid arthritis; RUNX2, runt-related transcription factor 2.