Functional Role of Chondrogenic Progenitor Cells in Rheumatoid Arthritis

Sabine Blaschke¹, Sandra Trautmann¹, Alexander W. Beham², Burkhard Mai³, Sebastian Koelling¹, Caroline Breysach⁴, Gabriele Wolf¹, Gerhard A. Mueller¹ and Nicolai Miosge⁵, ¹Nephrology & Rheumatology, University Medical Center Goettingen, Goettingen, Germany, ²Department of Surgery, Germany, ³Vitos Orthopaedic Clinic Kassel, Kassel, Germany, ⁴Department of Surgery, Goettingen, Germany, ⁵Dept. of Prosthodontics, Goettingen, Germany

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: bone metabolism, interleukins (IL), pathogenesis and stem cells, rheumatoid arthritis

Session Information

Title: Rheumamtoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease of still unknown etiology leading to progressive cartilage and bone destruction. Proinflammatory cytokines, immunoregulatory cells and synoviocytes were previously shown to play an important role in RA pathogenesis. Recently, a novel progenitor cell population, termed chondrogenic progenitor cells (CPCs), were isolated from repair tissue in later stages of osteoarthritis (OA). In this study, we analyzed the presence and functional characteristics of this cell type in human RA.

Methods:

Cartilage tissue specimens were obtained from 10 RA patients (age 44-85y) after total joint replacement surgery. All patients met the American College of Rheumatology criteria for established RA. The study was approved by the local ethics committee. CPCs were isolated as previously described (1) and subjected to flow cytometry and immunocytochemistry for stem cell surface markers and the interleukin-17 receptors (IL-17RA/RC). Expression of transcription factors was analyzed by quantitative RT-PCR and multipotency was characterized by in vitro chondrogenic, osteogenic and adipogenic differentiation. Functionally, in vitro effects of IL-17A/F-stimulation (50ng/ml for 24h) in RA-CPCs were assessed.

Results:

RA-CPCs could be isolated from tissue specimens in 10/10 RA cases. Flow cytometry revealed the expression of cell surface markers CD13, CD29, CD44, CD73, CD90 and CD105, but CPCs were negative for CD34 and CD45. Furthermore, RA-CPCs were shown to express the IL-17RA and -RC receptor. Transcription factors RUNX-2 and SOX-9 were detected by quantitative RT-PCR and immunocytochemistry. Multipotency differentiation revealed that RA-CPCs harbour a chondrogenic, osteogenic and adipogenic potential. In vitro stimulation with IL-17A/F resulted in significant upregulation of NF-kB, TRAF-6, MMP-3 and IL-6.

Conclusion:

Our study results demonstrate that CPCs are also present in RA cartilage tissue and express stem cell characteristics already described for OA-CPCs. Functional analysis revealed that these cells may also play a role in RA pathogenesis by IL-17-induced upregulation of MMP- and proinflammatory cytokine expression.

Disclosure:

S. Blaschke,
None;

S. Trautmann,
None;

A. W. Beham,
None;

B. Mai,
None;

S. Koelling,
None;

C. Breysach,
None;

G. Wolf,
None;

G. A. Mueller,
None;

N. Miosge,
None.

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