Sex differences of chondrogenic progenitor cells in late stages of osteoarthritis.
OBJECTIVE
Osteoarthritis (OA), a mainly degenerative disease, is known to be multifactorial in origin. Gene expression patterns vary between populations and sexes. Sex hormone receptors have been described in the cartilage tissue of animals and humans. We undertook this study to determine whether the regenerative potential of chondrogenic progenitor cells (CPCs) present in the arthritic tissue during the late stages of human OA might also be subject to sex-specific differences and influenced by sex steroids.


METHODS
We analyzed sex-specific differences in the regenerative potential of CPCs and the involvement of sex hormones in vitro in cartilage samples from patients with late-stage knee OA, using electrochemiluminescence immunoassay, microarray analysis, real-time reverse transcription-polymerase chain reaction, immunohistochemistry, Western blot analysis, fluorescence-activated cell sorting, and cell culture.


RESULTS
We detected expression of estrogen and testosterone in the OA synovial fluid as well as CPCs positive for estrogen receptor alpha (ERalpha), ERbeta, and androgen receptor. Both hormones influenced the expression of all 3 receptor genes as well as the chondrogenic potential of CPCs by regulating gene expression of Sox9, Runx2, type II collagen, and type I collagen. We found regulatory effects on the collagens via Sox9 and Runx2 as well as regulatory effects independent of these transcription factors. These effects were sex-specific and relied on hormone concentrations.


CONCLUSIONS
Physiologic concentrations of testosterone in men and premenopausal concentrations of estrogen in women have a positive effect on the chondrogenic potential of CPCs in vitro. Therefore, strategies of hormone replacement in the synovial fluid of women and men might have beneficial effects on the regenerative potential of arthritic cartilage tissue in late stages of human OA.
Koelling
Sebastian
S
Georg August University Goettingen, Goettingen, Germany.
Miosge
Nicolai
N
D000368:Aged; D002478:Cells, Cultured; D020219:Chondrogenesis; D017931:DNA Primers; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008593:Menopause / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics / Q000473:pathology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D013234:Stem Cells / Q000473:pathology*; D013739:Testosterone / Q000097:blood
D017931:DNA Primers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D013739:Testosterone; D004958:Estradiol; D012313:RNA