Inhibition of osteoclastogenesis by osteoblast-like cells genetically engineered to produce interleukin-10
| Autor: | Hiroyoshi Fujiwara, Yutaka Kawahito, Toshiro Yamamoto, Akika Ejima, Wataru Fujii, Kenta Yamamoto, Takahiro Seno, Aihiro Yamamoto, Masataka Kohno, Osam Mazda, Kazuki Fujioka, Ken Murakami, Ryo Oda, Tsunao Kishida |
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| Rok vydání: | 2015 |
| Předmět: |
Calcium Phosphates
Lipopolysaccharides musculoskeletal diseases medicine.medical_specialty medicine.medical_treatment Cell Cell- and Tissue-Based Therapy Biophysics Bone Matrix Osteoclasts Core Binding Factor Alpha 1 Subunit Inflammation Biochemistry Cell Line Bone remodeling Arthritis Rheumatoid Mice Calcification Physiologic Osteogenesis Transduction Genetic Osteoclast Internal medicine medicine Animals Bone Resorption Molecular Biology Osteoblasts Chemistry Macrophages RANK Ligand Cell Differentiation Osteoblast Cell Biology Interleukin-10 Cell biology RUNX2 Interleukin 10 Endocrinology medicine.anatomical_structure Cytokine Gene Expression Regulation Bone Remodeling medicine.symptom Genetic Engineering |
| Zdroj: | Biochemical and Biophysical Research Communications. 456:785-791 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2014.12.040 |
| Popis: | Bone destruction at inflamed joints is an important complication associated with rheumatoid arthritis (RA). Interleukin-10 (IL-10) may suppress not only inflammation but also induction of osteoclasts that play key roles in the bone destruction. If IL-10-producing osteoblast-like cells are induced from patient somatic cells and transplanted back into the destructive bone lesion, such therapy may promote bone remodeling by the cooperative effects of IL-10 and osteoblasts. We transduced mouse fibroblasts with genes for IL-10 and Runx2 that is a crucial transcription factor for osteoblast differentiation. The IL-10-producing induced osteoblast-like cells (IL-10-iOBs) strongly expressed osteoblast-specific genes and massively produced bone matrix that were mineralized by calcium phosphate in vitro and in vivo. Culture supernatant of IL-10-iOBs significantly suppressed induction of osteoclast from RANKL-stimulated Raw264.7 cells as well as LPS-induced production of inflammatory cytokine by macrophages. The IL-10-iOBs may be applicable to novel cell-based therapy against bone destruction associated with RA. |
| Databáze: | OpenAIRE |
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