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

نویسندگان

  • Martin Schicht
  • Jana Ernst
  • Andrea Nielitz
  • Lars Fester
  • Michael Tsokos
  • Saskia S Guddat
  • Lars Bräuer
  • Judith Bechmann
  • Karl-Stefan Delank
  • David Wohlrab
  • Friedrich Paulsen
  • Horst Claassen
چکیده

INTRODUCTION Sex 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. METHODS We 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. RESULTS Aromatase 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 10⁻⁷M 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. CONCLUSIONS We 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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Evaluation of CD98 Expression in Normal and Osteoarthritic Human Articular Chondrocytes

Background: Recent studies have provided evidence that integrins play roles in recognition of mechanical stimuli and its translation into a cellular response. Integrin signaling may be regulated by a number of mechanisms including accessory proteins such as CD98 (4F2 antigen). Objectives: To determine CD98 expression by human articular chondrocytes and its involvement in human articular mechano...

متن کامل

Production of sex steroid hormones from DHEA in articular chondrocyte of rats.

Dehydroepiandrosterone (DHEA), a precursor of sex steroid hormones, is synthesized by cholesterol side-chain cleavage cytochrome P-450 and 17alpha-hydroxylase cytochrome P-450 mainly from cholesterol and converted to testosterone and estrogen by 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-HSD, and aromatase cytochrome P-450. Although sex steroid hormones have important effects in the...

متن کامل

CD147 (Extracellular Matrix Metalloproteinase Inducer-EMMPRIN) Expression by Human Articular Chondrocytes

Background: Integrins are a family of transmembrane proteins that allow communication between the extracellular matrix and the interior of cells. Chondrocytes, cells of articular cartilage, express integrins and these molecules appear to have a variety of roles including mechanotransduction. Integrins are known to associate with a number of accessory molecules such as CD147 that may act to regu...

متن کامل

Costal Versus Articular Chondrocytes in Alginate Three-Dimensional Cultures

Given the difficulties in accessing articular cartilage as a source of chondrocytes to be used in fabricating cartilage constructs, alternative sources are required. The present study examined chondrocytes from costal cartilage for their suitability in cartilage tissue engineering. Chondrocytes isolated from rat knee and rib hyaline cartilage were separately mixed with alginate and placed in a ...

متن کامل

Quantitative Analysis of the Proliferation and Differentiation of Rat Articular Chondrocytes in Alginate 3D Culture

Background: While articular chondrocytes are among those appropriate candidates for cartilage regeneration, the cell dedifferentiation during monolayer culture has limited their application. Several investigations have indicated the usefulness of alginate, but the topic of proliferation and differentiation of chondrocytes in alginate culture has still remained controversial. Methods: Rat articu...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 16  شماره 

صفحات  -

تاریخ انتشار 2014