Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA.

• Authors: Jun Ishikawa, Nobunori Takahashi, Takuya Matsumoto, Yutaka Yoshioka, Noriyuki Yamamoto, Masaya Nishikawa, Hideharu Hibi, Naoki Ishigro, Minoru Ueda, Koichi Furukawa, Akihito Yamamoto
• Journal: Bone (Bone) Vol. 83 Pg. 210-219 (Feb 2016) ISSN: 1873-2763 [Electronic] United States
• PMID: 26603475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antibodies
• Antigens, CD
• Collagen Type II
• Culture Media, Conditioned
• SIGLEC9 protein, human
• Sialic Acid Binding Immunoglobulin-like Lectins

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Antibodies
• Antigens, CD (metabolism)
• Arthritis, Experimental (drug therapy, pathology)
• Arthritis, Rheumatoid (drug therapy, pathology)
• Child
• Collagen Type II (immunology)
• Culture Media, Conditioned (chemistry)
• Dental Pulp (cytology)
• Humans
• Inflammation (drug therapy, pathology)
• Injections, Intravenous
• Joints (drug effects, pathology)
• Macrophages (drug effects, pathology)
• Mice
• Osteoclasts (drug effects, pathology)
• Osteogenesis (drug effects)
• Sialic Acid Binding Immunoglobulin-like Lectins (metabolism)
• Stem Cells (metabolism)