Inhibition of osteoclastogenesis by osteoblast-like cells genetically engineered to produce interleukin-10
Inhibition of osteoclastogenesis by osteoblast-like cells genetically engineered to produce interleukin-10
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DOI：
10.1016/j.bbrc.2014.12.040
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发表时间：
2015-01-16
影响因子：
3.1
通讯作者：
Mazda, Osam
中科院分区：
文献类型：
--
作者：
Fujioka, Kazuki;Kishida, Tsunao;Mazda, Osam
炎症关节处的骨破坏是与类风湿性关节炎（RA）相关的重要并发症。白细胞介素10（IL-10）不仅可以抑制炎症，而且可以诱导破骨细胞，破骨细胞在骨破坏中起关键作用。如果从患者体细胞诱导产生IL-10的成骨细胞样细胞并移植回破坏性骨病变中，则这种治疗可能通过IL-10和成骨细胞的协同作用促进骨重建。我们用IL-10和Runx 2基因转导小鼠成纤维细胞，Runx 2是成骨细胞分化的关键转录因子。IL-10诱导的成骨样细胞（IL-10-iOBs）在体内外均能大量表达成骨细胞特异性基因，并能大量产生磷酸钙矿化的骨基质。IL-10-iOB的培养上清液显著抑制RANKL刺激的Raw264.7细胞对破骨细胞的诱导以及LPS诱导的巨噬细胞产生炎性细胞因子。IL 10-iOBs可能适用于针对与RA相关的骨破坏的新的基于细胞的疗法。(C)2014爱思唯尔公司All rights reserved.
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-10producing 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 IL10-iOBs may be applicable to novel cell-based therapy against bone destruction associated with RA. (C) 2014 Elsevier Inc. All rights reserved.