PUBLICATION

Mutant MAPK7-Induced Idiopathic Scoliosis is Linked to Impaired Osteogenesis

Authors
Zhou, T., Chen, C., Xu, C., Zhou, H., Gao, B., Su, D., Liao, Z., Li, Y., Yang, S., Su, P.
ID
ZDB-PUB-180723-2
Date
2018
Source
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology   48: 880-890 (Journal)
Registered Authors
Yang, Shulan
Keywords
HMSC, Idiopathic scoliosis, Mapk7, Osteogenesis, RPS6KA3, Zebrafish
MeSH Terms
  • Animals
  • Bone Marrow Cells/cytology
  • Cell Differentiation
  • Cells, Cultured
  • Down-Regulation
  • Embryo, Nonmammalian/metabolism
  • Fluoresceins/metabolism
  • Humans
  • Mesenchymal Stem Cells/cytology
  • Mesenchymal Stem Cells/metabolism
  • Mitogen-Activated Protein Kinase 7/antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 7/genetics*
  • Mitogen-Activated Protein Kinase 7/metabolism
  • Morpholinos/metabolism
  • Osteoblasts/cytology
  • Osteoblasts/metabolism
  • Osteogenesis*
  • Polymorphism, Single Nucleotide
  • RNA Interference
  • RNA, Small Interfering/metabolism
  • Ribosomal Protein S6 Kinases, 90-kDa/genetics
  • Ribosomal Protein S6 Kinases, 90-kDa/metabolism
  • Scoliosis/metabolism
  • Scoliosis/pathology*
  • Spinal Curvatures/diagnostic imaging
  • Spinal Curvatures/pathology
  • Zebrafish/growth & development
PubMed
30032135 Full text @ Cell Physiol. Biochem.
Abstract
Three rare MAPK7 variants that predispose individuals to adolescent idiopathic scoliosis have previously been identified. However, the mechanism underlying the effects of the mutations remain unknown.
Human mesenchymal stem cells (hMSCs) were isolated from both patients and healthy volunteer donors, and MAPK7 expression was detected by western blotting and real-time quantitative PCR (RT-qPCR). Zebrafish embryos were injected with mapk7 morpholinos or co-injected with morpholinos and wild-type (WT) MAPK7 messenger RNA (mRNA) at the one-cell stage, followed by calcein staining to evaluate bone formation. hMSCs were transfected with MAPK7 small interfering RNAs and osteogenesis was induced for 14 days. Alizarin red staining was performed and osteoblast markers were detected by western blotting and RT-qPCR. Since RPS6KA3 is a downstream target of MAPK7 and plays an important role in the osteogenesis, zebrafish embryos were then injected with rps6ka3 morpholinos, or co-injected with rps6ka3 or mapk7 morpholinos and WT RPS6KA3 mRNA at the one-cell stage.
MAPK7 expression in the patient group was much lower than in the control group. Morpholino-induced mapk7 knockdown in zebrafish embryos led to body curvature, which was significantly reversed by WT MAPK7 mRNA. Calcein staining revealed that mapk7-knockdown delayed the ossification of the vertebrae. MAPK7 silencing in hMSCs impaired osteogenesis and downregulated osteoblast marker expression. Morpholino-induced rps6ka3-knockdown in zebrafish embryos led to body curvature, which was reversed by WT RPS6KA3 mRNA. Interestingly, RPS6KA3 mRNA also partially reversed the phenotype induced by mapk7 morpholinos.
Impaired osteogenesis is linked to mutant MAPK7-induced idiopathic scoliosis , and RPS6KA3 may play an important role in this process.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes