Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Table 1 Interactions between long noncoding RNAs and epigenetic modifiers during osteogenic differentiation of mesenchymal stromal cells

LncRNAs	Samples	Expression	Epigenetic regulatory mechanisms	Target genes	Effects	Ref.
H19	hDPSCs	Up	Decreasing DNMT3B activity	DLX3	Promote odontogenic differentiation	Zeng et al[32]
H19	hDPSCs	Down	H19 was inhibited by the recruitment of DNMT3B and the enrichment of H3K9me3 in its promoter	miR-675 (derived from H19)	Inhibit odontogenic differentiation	Zeng et al[38]
H19	VICs	Up	H19 was upregulated by hypomethylation of its promoter	NR	Promote osteogenic differentiation	Hadji et al[40]
ANRIL	Umbilical cord	Down	ANRIL was inhibited by methylation of its promoter	NR	Decrease bone mass	Curtis et al[41]
HOTAIRM1	hDFSCs	Up	Inhibiting the recruitment of DNMT1	HOXA2	Promote osteogenic differentiation	Chen et al[17]
HOXA-AS3	hBMSCs	Up	Facilitating EZH2-mediated H3K27me3	RUNX2	Inhibit osteogenic differentiation	Zhu et al[62]
SNHG1	hPDLSCs	Up	Facilitating EZH2-mediated H3K27me3	KLF2	Inhibit osteogenic differentiation	Li et al[61]
OB1	human osteoblasts	Up	Inhibiting H3K27me3 by interacting with SUZ12 (a core part of PRC2)	Osterix	Promote osteogenic differentiation	Sun et al[58]

hDPSCs: Human dental pulp stromal cells; VICs: Valve interstitial cells; hDFSCs: Human dental follicle stromal cells; hBMSCs: Human bone marrow stromal cells; hPDLSCs: Human periodontal ligament stromal cells; NR: Not reported.

Table 2 Interactions between long noncoding RNAs and epigenetic modifiers during adipogenic differentiation of mesenchymal stromal cells

LncRNAs	Samples	Expression	Epigenetic regulatory mechanisms	Target genes	Effects	Ref.
HOTAIR	hBMSCs	Up	Interacting with DNMTs	NR	Inhibit adipogenic differentiation	Kalwa et al[46]
Plnc1	BMSCs	Up	Reducing the DNA methylation level	Ppar-γ2	Promote adipogenic differentiation	Zhu et al[49]
slincRAD	3T3-L1	Up	Facilitating the recruitment of Dnmt1	Cdkn1a	Promote adipogenic differentiation	Yi et al[50]
ADINR	hASCs	Up	Facilitating the recruitment of MLL3/4 complex (involved in the maintenance of H3K4me3 and the removal of H3K27me3) by binding PA1	C/EBP-α	Promote adipogenic differentiation	Xiao et al[63]
MIR31HG	hASCs	Down	Reducing the enrichment of AcH3 and H3K4me3	FABP4	Inhibit adipogenic differentiation	Huang et al[16]
H19	hBMSCs	Up	facilitating miR-675-mediated repression of HDACs	NR	Inhibit adipogenic differentiation	Huang et al[68]

hBMSCs: Human bone marrow stromal cells; BMSCs: Bone marrow stromal cells; hASCs: Human adipose-derived stromal cells; NR: Not reported.

Table 3 Interactions between long noncoding RNAs and epigenetic modifiers in degenerative bone diseases

LncRNAs	Samples	Expression	Epigenetic regulatory mechanisms	Target genes	Effects	Ref.
CTBP1-AS2	OA chondrocytes	Up	Increasing the methylation level of target gene	miR-130a	Decease proliferation rate of OA chondrocytes	Zhang et al[74]
XIST	OA chondrocytes	Up	Facilitating the recruitment of DNMT1, DNMT3A, and DNMT3B	TIMP-3	Raise collagen degradation in OA chondrocytes	Chen et al[76]
SNHG15	OA cartilage tissues	Down	SNHG15 was inhibited by methylation of its promoter	miR-7/KLF4	Affect ECM homeostasis	Chen et al[33]
SNHG9	OA chondrocytes	Down	Altering the methylation level of target gene	miR-34a	Affect apoptotic rate of chondrocytes	Zhang et al[80]
H19	UMR-106 and bone tissues from osteoporosis rat model	Down	H19 was inhibited by DNMT1-induced hypermethylation of its promoter	ERK-MAPK signaling-related genes	Impair osteogenic differentiation	Li et al[85]
MEG3	SMSCs	Up	Facilitating EZH2-mediated H3K27me3	TRIB2	Inhibit chondrogenic differentiation	You et al[87]

LncRNAs: Long noncoding RNAs; OA: Osteoarthritis; SMSCs: Synovium-derived mesenchymal stromal cells.