TABLE 6.

State of significance, experimental challenges and prospects of mRNA-, RNAi-and lncRNA-based therapy for bone osteogenesis.

RNA family	mRNA	miRNA	siRNA	lncRNA
State of significance	mRNA has shown to be an extremely useful tool to enhance osteogenesis in vivo and in vitro.	Both can negatively and positively regulate osteogenesis and bone differentiation in vivo and in vitro.		Although most functions are still not fully understood, some lncRNAs play vital roles in regulation of osteogenesis.
Experimental challenges	Chemical modification of the mRNAs is needed and as they have short half-life (low stability).	miRNA complex affected genes pathways.	More investigations are required on siRNA sequences to confirm the current findings.	The roles of lnRNAs are still not fully understood.
Prospects	- Enhancement of delivery methods - Further investigations of other mRNA sequences encoding osteogenesis enhancement genes is needed.	- CRISPR/Cas9 technology can be used to silence siRNA genes or targeted genes will less off target effect in a more time efficient manner - CRISPR/Cas9 can also aid in better understanding of some miRNA and siRNA functions in osteogenesis by knock-down/off experiments.		Limited information is available. Advancement in RNA sequencing technology will reveal more functional roles in bone formation applications.