Articular cartilage chondrocytes express aromatase and use enzymes involved in estrogen metabolism

Abstract

IntroductionSex hormones, especially estrogens, have been implicated in articular cartilage metabolism and the pathogenesis of postmenopausal osteoarthritis. The conversion by aromatase (CYP19A1) of androstenedione into estrone (E1) and of testosterone into 17β-estradiol (E2) plays a key role in the endogenous synthesis of estrogens in tissue.MethodsWe analyzed the expression of aromatase (CYP19A1) in immortalized C-28/I2 and T/C-28a2 chondrocytes, as well as in cultured primary human articular chondrocytes and human articular cartilage tissue, by means of RT-PCR, Western blotting and immunohistochemistry. By means of quantitative RT-PCR and enzyme-linked immunosorbent assay, we also determined whether the aromatase inhibitor letrozole influences estrogen metabolism of cultured chondrocytes in immortalized C-28/I2 chondrocytes.ResultsAromatase mRNA was detected in both immortalized chondrocyte cell lines, in cultured primary human chondrocytes, and in human articular cartilage tissue. By means of Western blot analysis, aromatase was detected at the protein level in articular cartilage taken from various patients of both sexes and different ages. Cultured primary human articular chondrocytes, C-28/I2 and T/C-28a2, and human articular cartilage tissue reacted with antibodies for aromatase. Incubation of C-28/I2 chondrocytes with 10−11 M to 10−7 M letrozole as an aromatase inhibitor revealed significantly increased amounts of the mRNAs of the enzyme cytochrome P4501A1 (CYP1A1), which is involved in the catagen estrogen metabolism, and of the estrogen receptors ER-α and ER-β. Concomitantly, synthesis of estrone (E1) was significantly downregulated after incubation with letrozole.ConclusionsWe demonstrate that human articular cartilage expresses aromatase at the mRNA and protein levels. Blocking of estrone synthesis by the aromatase inhibitor letrozole is counteracted by an increase in ER-α and ER-β. In addition, CYP1A1, an enzyme involved in catabolic estrogen metabolism, is upregulated. This suggests that articular chondrocytes use ERs functionally. The role of endogenous synthesized estrogens in articular cartilage health remains to be elucidated.

Screening of the Maturity Status of the Tibial Tuberosity by Ultrasonography in Higher Elementary School Grade Schoolchildren

“…All girls who had experienced menarche were in the epiphyseal stage and had significantly decreased cartilage thickness. Considering these findings together, the regression in the apophyseal cartilage at the tibial tuberosity in girls is thought to be accelerating when girls reach the epiphyseal stage and experience menarche, probably due to changes in the endocrine environment [26,27]. This phenomenon is also predicted to occur in boys, although the present study could not confirm it due to the lack of boys in the epiphyseal stage after the appearance of secondary sex characteristics.…”

Differential cytotoxic properties of drugs used for intra-articular injection on human chondrocytes

“…13,14 Cell lines offer the advantage of inter and intra-experimental comparability due to their stable characteristics, although they may lack several enzyme mechanisms, they are not embedded in their surrounding tissue and important cell repair mechanism may be absent when used in vitro. Our data demonstrate dose-dependent chondrotoxic effects of S-ketamine and bupivacaine.…”

Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men

“…Androstenedione is an important precursor for T, E2 and Ag production in non-gonadal tissues 11 . In human bone cells, the enzyme aromatase converts androstenedione and maintains longbone growth 12 . Animal studies have shown that androstenedione is associated with increasing bone mineral density at the metaphyseal and diaphyseal regions of the femur 13,14 , and bone mineral quality and quantity of cancellous and cortical bone 15 .…”