Steroid hormones strongly support bovine articular cartilage integration in the absence of interleukin-1beta.
OBJECTIVE
Posttraumatic integration of articular cartilage at fracture sites is essential for mechanical stability of cartilage, and ruptured cartilage is a prerequisite for early osteoarthritis. This study was undertaken to investigate effects on articular cartilage integration mediated by steroid hormones, interleukin-1beta (IL-1beta), and combinations thereof.


METHODS
Articular cartilage blocks were cultured in partial apposition for 2 weeks with ascorbic acid, testosterone, 17beta-estradiol, and dehydroepiandrosterone (DHEA), with or without IL-1beta. 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 microg/ml), the median adhesive strength was 49 kPa. In comparison with ascorbic acid alone, all steroid hormones induced a strong, concentration-dependent stimulation of integration (with maximum values observed with DHEA at 3 x 10(-5)M, testosterone at 10(-8)M, and 17beta-estradiol at 10(-11)M). For testosterone and 17beta-estradiol, this was also reflected by an increase of glycosaminoglycan content. Adhesive strength was increased with IL-1beta at 10 pg/ml, but not at 1 pg/ml or 100 pg/ml. In the presence of both IL-1beta and sex hormones, integration of articular cartilage was reduced.


CONCLUSIONS
This is the first study to demonstrate that steroid hormones such as 17beta-estradiol, DHEA, and testosterone stimulate articular cartilage integration. This effect is abrogated by low concentrations of IL-1beta. In the absence of IL-1beta or after neutralization of IL-1beta, steroid hormones might be favorable adjuvant compounds to optimize cartilage integration.
Englert
Carsten
C
University Hospital Regensburg, Regensburg, Germany.
Blunk
Torsten
T
Fierlbeck
Johann
J
Kaiser
Julia
J
Stosiek
Wolfgang
W
Angele
Peter
P
Hammer
Joachim
J
Straub
Rainer H
RH
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D013256:Steroids / Q000494:pharmacology*; D013264:Stifle; D013718:Tensile Strength / Q000187:drug effects / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology
D004338:Drug Combinations; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D013256:Steroids; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D001205:Ascorbic Acid