Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis

Toshio Takano, Yin Ji Li, Akiko Kukita, Takayoshi Yamaza, Yasunori Ayukawa, Kanako Moriyama, Norihisa Uehara, Hisayuki Nomiyama, Kiyoshi Koyano, Toshio Kukita

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) have potential to differentiate into multiple cell lineages. Recently, it was shown that MSCs also have anti-inflammatory and immunomodulatory functions. In this report, we investigated the regulatory function of MSCs in the development of inflammatory bone destruction in rats with adjuvant-induced arthritis (AA rats). MSCs were isolated from rat bone marrow tissues, expanded in the presence of basic FGF, and intraperitoneally injected into AA rats. MSC administration significantly suppressed inflammatory parameters: swelling score, swelling width, and thickness of hind paw. Radiographic evaluation indicated that MSC significantly suppressed bone destruction. Histological analysis showed that administration of MSCs markedly suppressed osteoclastogenesis in AA rats. To further delineate their effects on osteoclastogenesis, MSCs were added to in vitro bone marrow cultures undergoing osteoclastogenesis. MSCs significantly suppressed osteoclastogenesis in this system. Chemokine receptor expression in MSCs was assessed by RT-PCR, and a chemotactic assay was performed using a transwell culture system. MSCs showed significant chemotaxis to MIP-1α (CCL3) and SDF-1α (CXCL12), chemokines preferentially expressed in the area of inflammatory bone destruction. Furthermore, MSCs expressed IL-10 and osteoprotegerin, cytokines that suppress osteoclastogenesis. These data suggest that recruitment of MSC to the area of bone destruction in AA rats could suppress inflammatory bone destruction and raise the possibility that MSCs may have potential for the treatment of inflammatory bone destruction in arthritis.

Original languageEnglish
Pages (from-to)286-296
Number of pages11
JournalLaboratory Investigation
Volume94
Issue number3
DOIs
Publication statusPublished - Mar 1 2014

Fingerprint

Experimental Arthritis
Mesenchymal Stromal Cells
Bone and Bones
Osteogenesis
Bone Marrow
Chemokine CXCL12
Osteoprotegerin
Chemokine Receptors
Bone Development
Cell Lineage
Chemotaxis
Interleukin-10
Arthritis

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis. / Takano, Toshio; Li, Yin Ji; Kukita, Akiko; Yamaza, Takayoshi; Ayukawa, Yasunori; Moriyama, Kanako; Uehara, Norihisa; Nomiyama, Hisayuki; Koyano, Kiyoshi; Kukita, Toshio.

In: Laboratory Investigation, Vol. 94, No. 3, 01.03.2014, p. 286-296.

Research output: Contribution to journalArticle

@article{daa6ce5040a643fbb361f2129460b8ed,
title = "Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis",
abstract = "Mesenchymal stem cells (MSCs) have potential to differentiate into multiple cell lineages. Recently, it was shown that MSCs also have anti-inflammatory and immunomodulatory functions. In this report, we investigated the regulatory function of MSCs in the development of inflammatory bone destruction in rats with adjuvant-induced arthritis (AA rats). MSCs were isolated from rat bone marrow tissues, expanded in the presence of basic FGF, and intraperitoneally injected into AA rats. MSC administration significantly suppressed inflammatory parameters: swelling score, swelling width, and thickness of hind paw. Radiographic evaluation indicated that MSC significantly suppressed bone destruction. Histological analysis showed that administration of MSCs markedly suppressed osteoclastogenesis in AA rats. To further delineate their effects on osteoclastogenesis, MSCs were added to in vitro bone marrow cultures undergoing osteoclastogenesis. MSCs significantly suppressed osteoclastogenesis in this system. Chemokine receptor expression in MSCs was assessed by RT-PCR, and a chemotactic assay was performed using a transwell culture system. MSCs showed significant chemotaxis to MIP-1α (CCL3) and SDF-1α (CXCL12), chemokines preferentially expressed in the area of inflammatory bone destruction. Furthermore, MSCs expressed IL-10 and osteoprotegerin, cytokines that suppress osteoclastogenesis. These data suggest that recruitment of MSC to the area of bone destruction in AA rats could suppress inflammatory bone destruction and raise the possibility that MSCs may have potential for the treatment of inflammatory bone destruction in arthritis.",
author = "Toshio Takano and Li, {Yin Ji} and Akiko Kukita and Takayoshi Yamaza and Yasunori Ayukawa and Kanako Moriyama and Norihisa Uehara and Hisayuki Nomiyama and Kiyoshi Koyano and Toshio Kukita",
year = "2014",
month = "3",
day = "1",
doi = "10.1038/labinvest.2013.152",
language = "English",
volume = "94",
pages = "286--296",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis

AU - Takano, Toshio

AU - Li, Yin Ji

AU - Kukita, Akiko

AU - Yamaza, Takayoshi

AU - Ayukawa, Yasunori

AU - Moriyama, Kanako

AU - Uehara, Norihisa

AU - Nomiyama, Hisayuki

AU - Koyano, Kiyoshi

AU - Kukita, Toshio

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Mesenchymal stem cells (MSCs) have potential to differentiate into multiple cell lineages. Recently, it was shown that MSCs also have anti-inflammatory and immunomodulatory functions. In this report, we investigated the regulatory function of MSCs in the development of inflammatory bone destruction in rats with adjuvant-induced arthritis (AA rats). MSCs were isolated from rat bone marrow tissues, expanded in the presence of basic FGF, and intraperitoneally injected into AA rats. MSC administration significantly suppressed inflammatory parameters: swelling score, swelling width, and thickness of hind paw. Radiographic evaluation indicated that MSC significantly suppressed bone destruction. Histological analysis showed that administration of MSCs markedly suppressed osteoclastogenesis in AA rats. To further delineate their effects on osteoclastogenesis, MSCs were added to in vitro bone marrow cultures undergoing osteoclastogenesis. MSCs significantly suppressed osteoclastogenesis in this system. Chemokine receptor expression in MSCs was assessed by RT-PCR, and a chemotactic assay was performed using a transwell culture system. MSCs showed significant chemotaxis to MIP-1α (CCL3) and SDF-1α (CXCL12), chemokines preferentially expressed in the area of inflammatory bone destruction. Furthermore, MSCs expressed IL-10 and osteoprotegerin, cytokines that suppress osteoclastogenesis. These data suggest that recruitment of MSC to the area of bone destruction in AA rats could suppress inflammatory bone destruction and raise the possibility that MSCs may have potential for the treatment of inflammatory bone destruction in arthritis.

AB - Mesenchymal stem cells (MSCs) have potential to differentiate into multiple cell lineages. Recently, it was shown that MSCs also have anti-inflammatory and immunomodulatory functions. In this report, we investigated the regulatory function of MSCs in the development of inflammatory bone destruction in rats with adjuvant-induced arthritis (AA rats). MSCs were isolated from rat bone marrow tissues, expanded in the presence of basic FGF, and intraperitoneally injected into AA rats. MSC administration significantly suppressed inflammatory parameters: swelling score, swelling width, and thickness of hind paw. Radiographic evaluation indicated that MSC significantly suppressed bone destruction. Histological analysis showed that administration of MSCs markedly suppressed osteoclastogenesis in AA rats. To further delineate their effects on osteoclastogenesis, MSCs were added to in vitro bone marrow cultures undergoing osteoclastogenesis. MSCs significantly suppressed osteoclastogenesis in this system. Chemokine receptor expression in MSCs was assessed by RT-PCR, and a chemotactic assay was performed using a transwell culture system. MSCs showed significant chemotaxis to MIP-1α (CCL3) and SDF-1α (CXCL12), chemokines preferentially expressed in the area of inflammatory bone destruction. Furthermore, MSCs expressed IL-10 and osteoprotegerin, cytokines that suppress osteoclastogenesis. These data suggest that recruitment of MSC to the area of bone destruction in AA rats could suppress inflammatory bone destruction and raise the possibility that MSCs may have potential for the treatment of inflammatory bone destruction in arthritis.

UR - http://www.scopus.com/inward/record.url?scp=84896873337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896873337&partnerID=8YFLogxK

U2 - 10.1038/labinvest.2013.152

DO - 10.1038/labinvest.2013.152

M3 - Article

C2 - 24395111

AN - SCOPUS:84896873337

VL - 94

SP - 286

EP - 296

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 3

ER -