Role of mesenchymal stem cell-derived exosomal non-coding RNAs in bone and bone-related disorders

Table 1 Role of exosomal non-coding RNAs in bone homeostasis, key targets, and functional effects

Exosome origin	Exosomal ncRNAs	Targets/pathways	Effects	In vivo models	Ref.
BMSCs	miR-150-5p	SOX2 and PI3K/Akt pathway	Induced type H blood vessel angiogenesis and osteogenesis	Female mice	[36]
Fucoidan-induced MSCs	miR-146b-5p	TRAF6 and PI3K/Akt/mTOR pathways	Suppressed inflammatory responses, extracellular matrix degradation, and promoted chondrocyte autophagy	Male Sprague-Dawley rats	[37]
BMSCs	miR-422a	KLK4	Inhibited angiogenesis and osteogenesis	Female mice	[38]
Synovial MSCs	miR-485-3p	NRP1 and PI3K/Akt pathway	Relieved cartilage damage	N/A	[39]

ncRNAs: Non-coding RNAs; BMSCs: Bone marrow mesenchymal stem cells; MSCs: Mesenchymal stem cells; SOX2: SRY (Sex Determining Region) box 2; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B; TRAF6: Tumor necrosis factor receptor-associated factor 6; mTOR: Mechanistic target of rapamycin; KLK4: Kallikrein-4; NRP1: Neuropilin 1; N/A: Not applicable.

Table 2 The role of mesenchymal stem cell-derived exosomal non-coding RNAs in the pathophysiology of bone-related disorders

Diseases	Sources	Exosomal ncRNAs	Targets	Signaling pathways involved	Effects	Ref.
OA	BMSCs	lncRNA TUC339	-	-	Mitigated OA by promoting the transition from M1-type to M2-type macrophage polarization, inhibiting inflammation, and enhancing chondrocyte function	[44]
	MSCs	lncRNA KLF3-AS1	-	-	Alleviated OA by promoting chondrocyte proliferation and inhibiting apoptosis, thereby facilitating cartilage repair	[45]
	BMSCs	miR-9-5p	3’ UTR of syndecan-1	-	Reduced inflammatory markers, decreased oxidative stress, and suppressed expression of OA-associated factors	[46]
	BMSCs	miR-135b	-	Downregulation of MAPK6 expression	Promoted M2 polarization of synovial macrophages thereby aiding in cartilage healing	[47]
	Adipose MSCs	miR-376c-3p	3’ UTR of Wnt family member 3 or Wnt family member 9a	Hindering of Wnt/β-catenin pathway	Induced chondrocyte degradation and synovial fibrosis	[48]
	Synovial MSCs	miR-320c	-	Modulation of ADAM metalloproteinase domain 19-dependent Wnt signaling	Inhibited extracellular matrix degradation and chondrocyte apoptosis	[49]
	BMSCs	circRNA_0001236	miR-3677-3p	-	Increased the collagen type II alpha 1 chain and sex-determining region Y-box 9 expression and reduced the matrix metalloproteinase-13 expression	[50]
	Umbilical cord blood MSCs	lncRNA H19	miR-29a-3p	-	Decreased the phosphorylation levels of biochemical markers of neuropathic pain (NR1, NR2B, protein kinase C gamma and ERK) in astrocytes	[51]
OP	Human BMSCs	miR-186	MOB kinase activator 1A	Hippo pathway	Facilitated osteogenesis in postmenopausal OP	[52]
OS	BMSCs	lncRNA PVT1	miR-183-5p	-	Enhanced OS proliferation and migration	[43]

MSCs: Mesenchymal stem cells; BMSCs: Bone marrow mesenchymal stem cells; OA: Osteoarthritis; OP: Osteoporosis; OS: Osteosarcoma; KLF3: Kruppel-like factor 3; AS1: Antisense RNA 1; UTR: Untranslated region; Wnt: Wingless/integrated; MAPK6: Mitogen-activated protein kinase; ADAM: A disintegrin and metalloprotease; ERK: Extracellular signal-related kinase.