miR-29b negatively regulates human osteoclastic cell differentiation and function: Implications for the treatment of multiple myeloma-related bone disease

Marco Rossi, Maria Rita Pitari, Nicola Amodio, Maria Teresa Di Martino, Francesco Conforti, Emanuela Leone, Cirino Botta, Francesco Maria Paolino, Teresa Del Giudice, Eleonora Iuliano, Michele Caraglia, Manlio Ferrarini, Antonio Giordano, Pierosandro Tagliaferri, Pierfrancesco Tassone

Research output: Contribution to journalArticlepeer-review

Abstract

Skeletal homeostasis relies upon a fine tuning of osteoclast (OCL)-mediated bone resorption and osteoblast (OBL)-dependent bone formation. This balance is unsettled by multiple myeloma (MM) cells, which impair OBL function and stimulate OCLs to generate lytic lesions. Emerging experimental evidence is disclosing a key regulatory role of microRNAs (miRNAs) in the regulation of bone homeostasis suggesting the miRNA network as potential novel target for the treatment of MM-related bone disease (BD). Here, we report that miR-29b expression decreases progressively during human OCL differentiation in vitro. We found that lentiviral transduction of miR-29b into OCLs, even in the presence of MM cells, significantly impairs tartrate acid phosphatase (TRAcP) expression, lacunae generation, and collagen degradation, which are relevant hallmarks of OCL activity. Accordingly, expression of cathepsin K and metalloproteinase 9 (MMP9) as well as actin ring rearrangement were impaired in the presence of miR-29b. Moreover, we found that canonical targets C-FOS and metalloproteinase 2 are suppressed by constitutive miR-29b expression which also downregulated the master OCL transcription factor, NAFTc-1. Overall, these data indicate that enforced expression of miR-29b impairs OCL differentiation and overcomes OCL activation triggered by MM cells, providing a rationale for miR-29b-based treatment of MM-related BD.

Original languageEnglish
Pages (from-to)1506-1515
Number of pages10
JournalJournal of Cellular Physiology
Volume228
Issue number7
DOIs
Publication statusPublished - Jul 2013

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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