Actin-binding LIM protein 1 regulates receptor activator of NF-κB ligand-mediated osteoclast differentiation and motility

Autor: Seoung Hoon Lee, Su Hyun Jin, Young Rae Lee, Hyunsoo Kim, Yongwon Choi, Dong Ryun Gu, Keun Ha Park
Rok vydání: 2018
Předmět:
rac1 GTP-Binding Protein
musculoskeletal diseases
0301 basic medicine
Osteoclasts
Bone Marrow Cells
RAC1
Biochemistry
Mice
Phosphatidylinositol 3-Kinases
03 medical and health sciences
Cell Movement
Osteoclast
medicine
Animals
RNA
Small Interfering
Molecular Biology
Transcription factor
Protein kinase B
Cells
Cultured
PI3K/AKT/mTOR pathway
NFATC Transcription Factors
ABLIM1
030102 biochemistry & molecular biology
biology
Activator (genetics)
Chemistry
Microfilament Proteins
Neuropeptides
RANK Ligand
RANKL
Cell Differentiation
Motility
Articles
General Medicine
LIM Domain Proteins
Cell biology
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
biology.protein
RNA Interference
Signal transduction
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-fos
Signal Transduction
LIM domain
Zdroj: BMB Reports
ISSN: 1976-670X
DOI: 10.5483/bmbrep.2018.51.7.106
Popis: Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, mediates interactions between actin filaments and cytoplasmic targets. However, the role of ABLIM1 in osteoclast and bone metabolism has not been reported. In the present study, we investigated the role of ABLIM1 in the receptor activator of NF-κB ligand (RANKL)- mediated osteoclastogenesis. ABLIM1 expression was induced by RANKL treatment and knockdown of ABLIM1 by retrovirus infection containing Ablim1-specific short hairpin RNA (shAblim1) decreased mature osteoclast formation and bone resorption activity in a RANKL-dose dependent manner. Coincident with the downregulated expression of osteoclast differentiation marker genes, the expression levels of c-Fos and the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), critical transcription factors of osteoclastogenesis, were also decreased in shAblim1-infected osteoclasts during RANKLmediated osteoclast differentiation. In addition, the motility of preosteoclast was reduced by ABLIM1 knockdown via modulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/Rac1 signaling pathway, suggesting another regulatory mechanism of ABLIM1 in osteoclast formation. These data demonstrated that ABLIM1 is a positive regulator of RANKLmediated osteoclast formation via the modulation of the differentiation and PI3K/Akt/Rac1-dependent motility. [BMB Reports 2018; 51(7): 356-361].
Databáze: OpenAIRE
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