Myofibroblast Accumulation Correlates with the Formation of Fibrotic Tissue in a Rat Air Pouch Model

ANETTE BJÄRDAHLEN, PER-OLA ÖNNERVIK, GUNILLA WESTERGREN-THORSSON, ANDERS MALMSTRÖM, and BENGT SÄRNSTRAND

ABSTRACT.

Objective. The pathogenesis of arthritic joints involves cartilage degradation and pannus formation. It is well known that pannus influences the cartilage; however, the mechanism behind how the degrading cartilage interacts with pannus is not well known. To investigate this interplay, the expression of extracellular matrix (ECM) components in pannus and the degrading cartilage was analyzed.

Methods. Studies were performed using a rat air pouch model where cotton with viable or killed cartilage was implanted into 7-day-old pouches for 1-28 days. The remodeling of cartilage and the formation of tissue in the cotton was characterized histologically by quantitation of infiltrated cells. The amounts of collagen, hyaluronan, and proteoglycan were estimated.

Results. Implantation of homologous femoral head cartilage in cotton resulted in extensive remodeling of cartilage and formation of ECM in the cotton. In cotton without cartilage, fibroblasts and myofibroblasts were the predominant cells in the early stage of analyses. The ECM formed in cotton was of a fibrotic type, with mainly collagen and smaller amounts of proteoglycans correlating to the presence of myofibroblasts. In the cotton with cartilage, however, inflammatory cells such as neutrophils, macrophages, and lymphocytes dominated. Delayed accumulation of collagen and increased synthesis of proteoglycans occurred early in cotton with viable as well as non-viable cartilage. In later stages, the cell pattern changed and the myofibroblasts emerged together with an increasing collagen formation.

Conclusion. The interaction between cartilage and the newly formed granulation tissue results in a faster degradation of cartilage molecules, which in turn leak into the surrounding ECM and affect the recruitment of myofibroblasts. This indicates the importance of the micromatrix. (J Rheumatol 2002;29:1698-707)

Key Indexing Terms:

AIR POUCH
ARTHRITIS
CARTILAGE
MYOFIBROBLAST
PANNUS
PROTEOGLYCAN

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From the Department of Cell and Molecular Biology, Biomedical Centre, University of Lund; and Department of Bioscience and Experimental Medicine, AstraZeneca AB, Lund, Sweden.

Supported by grants from the Medical Research Council, Riksförbundet mot reumatism, Johan and Greta Kocks Foundation, Alfred Österlunds Foundation, Gustaf V 80 årsfond, the Medical Faculty of Lund, AstraZeneca R&D, and Crafoords Foundation.

A. Bjärdahlen, Dr Med Sci; G. Westergren-Thorsson, DrMedSci, Associate Professor; A. Malmström, PhD, Professor, Department of Cell and Molecular Biology, Biomedical Centre, University of Lund; P-O. Önnervik, BSc, Department of Bioscience; B. Särnstrand, DrMedSci, Department of Experimental Medicine, AstraZeneca.

Address reprint requests to Dr. A. Bjärdahlen, Department of Cell and Molecular Biology, C13 Biomedical Centre, University of Lund, S-221 84 Lund, Sweden. E-mail: anette.bjardahlen@medkem.lu.se

Submitted August 16, 2001; revision accepted January 9, 2002.

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