Secretomes from mesenchymal stem cells participate in the regulation of osteoclastogenesis in vitro

Kenichi Ogata, Wataru Katagiri, Hideharu Hibi

研究成果: Contribution to journalArticle査読

16 被引用数 (Scopus)

抄録

Objectives: The receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are novel clinically effective agents that inhibit osteoclast differentiation, function, and survival by binding to RANKL. Medication-related osteonecrosis of the jaw (MRONJ), caused as a result of treatment using denosumab, is a newly emerging type of bone necrosis, the exact pathogenesis of which is unknown. Several studies recently showed that the intravenous administration of mesenchymal stem cells (MSCs) improved the osteonecrosis of the jaw, and it was hypothesized that paracrine effects by secretomes from MSCs are the main constituent. Our aim was to investigate the effects of serum-free conditioned media from human MSCs (MSC-CM) and RANKL inhibitors on osteoclast differentiation. Materials and methods: Cytokines included in MSC-CM were identified using the cytokine array analysis. MSC-CM was added to the culture medium of rat osteoclast precursors containing RANKL inhibitor. Osteoclast differentiation assays, immunohistochemistry, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, and pit formation assays were performed. Results: MSC-CM included various cytokines such as the recruitment of cell osteogenesis angiogenesis and cell proliferation. MSC-CM promoted osteoclast differentiation and expression of master regulatory transcriptional factors for osteoclastogenesis. In addition, MSC-CM showed function maintenance in osteoclasts despite the presence of RANKL inhibitors. Conclusions: Our findings suggest that secretomes in MSC-CM were related to the regulation of osteoclast differentiation, which may reduce the effect of RANKL inhibitors. Clinical relevance: New combinations of drugs using factors included in MSC-CM have effective therapeutic modality for treating patients with MRONJ.

本文言語英語
ページ(範囲)1979-1988
ページ数10
ジャーナルClinical Oral Investigations
21
6
DOI
出版ステータス出版済み - 7 1 2017

All Science Journal Classification (ASJC) codes

  • 歯科学(全般)

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