ARTHRITIS & RHEUMATISM Vol. 54, No. 12, December 2006, pp 3890–3897 DOI 10.1002/art.22250 © 2006, American College of Rheumatology Steroid Hormones Strongly Support Bovine Articular Cartilage Integration in the Absence of Interleukin-1 Carsten Englert, 1 Torsten Blunk, 1 Johann Fierlbeck, 2 Julia Kaiser, 1 Wolfgang Stosiek, 1 Peter Angele, 1 Joachim Hammer, 2 and Rainer H. Straub 1 Objective. Posttraumatic integration of articular cartilage at fracture sites is essential for mechanical stability of cartilage, and ruptured cartilage is a prereq- uisite for early osteoarthritis. This study was under- taken to investigate effects on articular cartilage inte- gration mediated by steroid hormones, interleukin-1 (IL-1), and combinations thereof. Methods. Articular cartilage blocks were cultured in partial apposition for 2 weeks with ascorbic acid, testosterone, 17-estradiol, and dehydroepiandros- terone (DHEA), with or without IL-1. Mechanical integration was measured as adhesive strength, i.e., the maximum force at rupture of integrated cartilage blocks divided by the overlap area. Glycosaminoglycan content was used to study synthesized extracellular matrix. Results. Culture in medium without supplements did not lead to integration (adhesive strength 0 kPa). With administration of ascorbic acid (100 g/ml), the median adhesive strength was 49 kPa. In comparison with ascorbic acid alone, all steroid hormones induced a strong, concentration-dependent stimulation of integra- tion (with maximum values observed with DHEA at 3  10 5 M, testosterone at 10 8 M, and 17-estradiol at 10 11 M). For testosterone and 17-estradiol, this was also reflected by an increase of glycosaminoglycan con- tent. Adhesive strength was increased with IL-1 at 10 pg/ml, but not at 1 pg/ml or 100 pg/ml. In the presence of both IL-1 and sex hormones, integration of articular cartilage was reduced. Conclusion. This is the first study to demonstrate that steroid hormones such as 17-estradiol, DHEA, and testosterone stimulate articular cartilage integra- tion. This effect is abrogated by low concentrations of IL-1. In the absence of IL-1 or after neutralization of IL-1, steroid hormones might be favorable adjuvant compounds to optimize cartilage integration. New concepts are needed for early treatment of posttraumatic cartilage lesions in order to support inte- grative cartilage repair. Inadequate integration at cartilage–cartilage interfaces can lead to fibrillation and degeneration of surrounding tissue (1). This may be one of the prerequisites for development of osteoarthritis, in which a shift from anabolic to catabolic cartilage metab- olism has been described to occur (2,3). The secretion of catabolic cytokines from cartilage is responsible for this catabolic transformation (4,5). Catabolic cytokines such as interleukin-1 (IL-1) have detrimental effects on the composition and mechanical properties of articular car- tilage (2,6). Steroid hormones such as dehydroepiandros- terone (DHEA) have been shown to counterbalance catabolic chondrocyte metabolism (7). In addition, ste- roid hormones have been found to counteract pro- inflammatory effects of catabolic cytokines such as IL- 1, tumor necrosis factor, and IL-6 (8,9). Posttraumatic cartilage repair might be supported by anabolic stimu- lation of the interface tissue when the fracture is surgi- cally trimmed and stabilized (10). In vitro experiments have demonstrated some factors, such as presence of viable cells at integration sites (11) and adequate colla- gen metabolism and collagen deposition (12,13), that are Supported by an intramural research grant (ReForM C “Artikula ¨re Grenzfla ¨chen”) from University Hospital Regensburg. 1 Carsten Englert, MD, Torsten Blunk, PhD, Julia Kaiser, Wolfgang Stosiek, Peter Angele, MD, Rainer H. Straub, MD: Univer- sity Hospital Regensburg, Regensburg, Germany; 2 Johann Fierlbeck, Dipl-Ing, Joachim Hammer, Dr-Ing: University of Applied Science Regensburg, Regensburg, Germany. Address correspondence and reprint requests to Rainer H. Straub, MD, Professor of Experimental Medicine, Department of Internal Medicine I, University Hospital Regensburg, 93042 Regens- burg, Germany. E-mail: rainer.straub@klinik.uni-regensburg.de. Submitted for publication March 9, 2006; accepted in revised form August 24, 2006. 3890