1. miR-29b negatively regulates human osteoclastic cell differentiation and function: Implications for the treatment of multiple myeloma-related bone disease
- Author
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Eleonora Iuliano, Pierfrancesco Tassone, Michele Caraglia, Antonio Giordano, Francesco Maria Paolino, Cirino Botta, Manlio Ferrarini, Pierosandro Tagliaferri, Maria Teresa Di Martino, Maria Rita Pitari, Emanuela Leone, Francesco Conforti, Nicola Amodio, Teresa Del Giudice, Marco Rossi, Rossi M., Pitari M.R., Amodio N., Di Martino M.T., Conforti F., Leone E., Botta C., Paolino F.M., Del Giudice T., Iuliano E., Caraglia M., Ferrarini M., Giordano A., Tagliaferri P., Tassone P., Rossi, M, Pitari, Mr, Amodio, N, Di Martino, Mt, Conforti, F, Leone, E, Botta, C, Paolino, Fm, Del Giudice, T, Iuliano, E, Caraglia, Michele, Ferrarini, M, Giordano, A, Tagliaferri, P, and Tassone, P.
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Bone disease ,Physiology ,Cellular differentiation ,Cathepsin K ,Clinical Biochemistry ,Gene Expression ,Osteoclasts ,Osteolysis ,MMP9 ,Cells, Cultured ,Tartrate-resistant acid phosphatase ,Tumor ,Cultured ,Receptor Activator of Nuclear Factor-kappa B ,Genes, fos ,Cell Differentiation ,Osteoblast ,Cell biology ,Isoenzymes ,multiple myeloma ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,osteoclast ,Matrix Metalloproteinase 2 ,medicine.medical_specialty ,fos ,Cells ,Acid Phosphatase ,Biology ,Collagen Type I ,Bone resorption ,Cell Line ,Osteoclast ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Bone Resorption ,Osteoblasts ,microRNA ,NFATC Transcription Factors ,Tartrate-Resistant Acid Phosphatase ,miR-29b ,Cell Biology ,medicine.disease ,Actins ,MicroRNAs ,Endocrinology ,Genes ,Multiple Myeloma - Abstract
Skeletal homeostasis relies upon a fine tuning of osteoclast (OCLs)-mediated bone resorption and osteoblast (OBLs)-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. 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 bone disease. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
- Published
- 2013
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