Lab Invest. 2014 Mar;94(3):286-96.

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

Takano T1, Li YJ2, Kukita A3, Yamaza T2, Ayukawa Y4, Moriyama K2, Uehara N2, Nomiyama H5, Koyano K4, Kukita T2.
  • 1Department of Molecular Cell Biology & Oral Anatomy, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan [2] Department of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
  • 2Department of Molecular Cell Biology & Oral Anatomy, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
  • 3Department of Microbiology, Faculty of Medicine, Saga University, Saga, Japan.
  • 4Department of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
  • 5Department of Molecular Enzymology, Kumamoto University, Graduate School of Medical Science, Kumamoto, Japan.

 

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.

PMID: 24395111

 

Supplementary information

Mesenchymal stem cells (MSCs) are multipotent stem cells bearing the ability to differentiate into various cells of mesenchymal origin. MSCs also have potential to differentiate into neurons and lung cells (1). In addition to their fundamental potential in regenerative medicine as the excellent cell source, MSCs have recently been recognized as the important modulator of immune responses (2). Here we demonstrate a successful suppression of inflammatory bone destruction by the injected MSCs in the system of adjuvant-induced arthritis in rats. Bone marrow derived MSCs express receptors for chemotactic factors (SDF-1a and MIP1-a) and migrate toward these factors, which are expressed in the sites of bone destruction (Figure 1) (3). As these MSCs express inhibitory cytokines (OPG and IL-10) on osteoclastogenesis (Figure 2), MSCs recruited to the sites of inflammation through the chemotactic system are supposed to suppress efficiently the osteoclastogenesis at the sites of inflammatory bone destruction.

(1) Ucceli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nature Rev. Immunol. 8:726-736, 2008.

(2) Nauta A.J., Fibbe W.E. Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499-3506, 2007.

(3) Toh K., Kukita T, Wu Z. Kukita A., Sandra F., Tang Q.Y., Nomiyama H., Iijima T. Possible involvement of MIP-1alpha in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis. Lab. Invest. 84:1092-1102, 2004.

 

 

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