TRPM3/TRPV4 regulates Ca2+-mediated RANKL/NFATc1 expression in osteoblasts

Aran Son, Namju Kang, Jung Yun Kang, Ki Woo Kim, Yu Mi Yang, Dong Min Shin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mechanical stress plays an important role in the regulation of bone turnover. However, the mechanism underlying hypo-osmotic stress-induced cellular response in osteoblasts remains poorly understood. In this study, we investigated the effect of hypotonic stress on the expression of bone remodeling factors, including the receptor activator of nuclear factor-kappa B ligand (RANKL) and the nuclear factor of activated T cells type c1 (NFATc1) in primary mouse osteoblasts and MC3T3-E1 cells. Hypo-osmotic stress induced significant increases in RANKL mRNA expression and intracellular Ca2+ concentration ([Ca2+]i) from the extracellular space. Hypo-osmotic stress-induced effects on [Ca2+]i and RANKL and NFATc1 protein expression were decreased by antagonists of transient receptor potential melastatin 3 (TRPM3) and vanilloid 4 (TRPV4). Agonists of TRPM3 and TRPV4 activated [Ca2+]i and RANKL and NFATc1 protein expression. Furthermore, genetic suppression of Trpm3 and Trpv4 reduced hypo-osmotic stress-induced effects in mouse osteoblasts. These results suggest that hypo-osmotic stress induces increases in [Ca2+]i through TRPM3 and TRPV4 to regulate RANKL and NFATc1 expression in mouse osteoblastic cells and that mechanical stress-activated TRP channels may play a critical role in bone remodeling.

Original languageEnglish
Pages (from-to)207-218
Number of pages12
JournalJournal of molecular endocrinology
Volume61
Issue number4
DOIs
Publication statusPublished - 2018 Nov

Fingerprint

RANK Ligand
NFATC Transcription Factors
Osmotic Pressure
Osteoblasts
Bone Remodeling
Mechanical Stress
Genetic Suppression
Extracellular Space
Proteins
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Cite this

Son, Aran ; Kang, Namju ; Kang, Jung Yun ; Kim, Ki Woo ; Yang, Yu Mi ; Shin, Dong Min. / TRPM3/TRPV4 regulates Ca2+-mediated RANKL/NFATc1 expression in osteoblasts. In: Journal of molecular endocrinology. 2018 ; Vol. 61, No. 4. pp. 207-218.
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TRPM3/TRPV4 regulates Ca2+-mediated RANKL/NFATc1 expression in osteoblasts. / Son, Aran; Kang, Namju; Kang, Jung Yun; Kim, Ki Woo; Yang, Yu Mi; Shin, Dong Min.

In: Journal of molecular endocrinology, Vol. 61, No. 4, 11.2018, p. 207-218.

Research output: Contribution to journalArticle

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