Lumbar Disc Degeneration is Facilitated by MiR-100-Mediated FGFR3 Suppression.
OBJECTIVE
The pathogenesis of lumbar disc degeneration (LDD) involved activation of matrix metalloproteinase 13 (MMP13) by differential expression of fibroblast growth factor receptor 1 (FGFR1) and FGFR3. Nevertheless, the molecular regulation of FGFR1 and FGFR3 in the lumber disc cells remains elusive.


METHODS
We examined the FGFR1 and FGFR3 levels and microRNAs (miRNAs) levels in the resected LDD discs, compared to the traumatized, non-LDD discs. We analyzed the binding of miR-100 to the 3'UTR of FGFR3 mRNA and its effects on FGFR3 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-100 levels in a human nucleus pulposus SV40 cell line (HNPSV), and examined the effects on the expression of FGFR3 and MMP13, by RT-qPCR, Western blot and ELISA.


RESULTS
The levels of FGFR1 and miR-100 were significantly higher, while the levels of FGFR3 were significantly lower, in LDD discs, compared to the control non-LDD discs. The levels of FGFR3, but not the levels of FGFR1, inversely correlated with the levels of miR-100. Moreover, miR-100 was found to bind to the 3'UTR of FGFR3 mRNA to prevent its translation. In miR-100-modified HNPSV cells, we found that miR-100 decreased FGFR3 levels, and increased MMP13 levels.


CONCLUSIONS
miR-100 may activate MMP13 through 3'UTR-suppressoin of FGFR3 mRNA to facilitate development of LDD.
Orthopedic Department, Shanghai 10th People's Hospital, Tongji University School of Medcine, Shanghai, China.
Ning
N
Yan
Shunzhi
S
Yu
Hailong
H
Zhang
Tiesheng
T
Hou
D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000473:pathology*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; C544266:MIRN100 microRNA, human; D035683:MicroRNAs; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13