17β-estradiol reduces expression of MMP-1, -3, and -13 in human primary articular chondrocytes from female patients cultured in a three dimensional alginate system

Abstract

Clinical observations have suggested a relationship between osteoarthritis and a changed sex-hormone metabolism, especially in menopausal women. This study analyzes the effect of 17β-estradiol on expression of matrix metalloproteinases-1, -3, -13 (MMP-1, -3, -13) and tissue inhibitors of metalloproteinases-1, -2 (TIMP-1, -2) in articular chondrocytes. An imbalance of matrix metalloproteinases (MMPs) specialized on degradation of articular cartilage matrix over the respective inhibitors of these enzymes (TIMPs) that leads to matrix destruction was postulated in the pathogenesis of osteoarthritis. Primary human articular chondrocytes from patients of both genders were cultured in alginate beads at 5% O(2) to which 10(-11)M-10(-5)M 17β-estradiol had been added and analyzed by means of immunohistochemistry, immunocytochemistry and real-time RT-PCR. Since articular chondrocytes in vivo are adapted to a low oxygen tension, culture was performed at 5% O(2). Immunohistochemical staining in articular cartilage tissue from patients and immunocytochemical staining in articular chondrocytes cultured in alginate beads was positive for type II collagen, estrogen receptor α, MMP-1, and -13. It was negative for type I collagen, MMP-3, TIMP-1 and -2. Using real-time RT-PCR, it was demonstrated that physiological and supraphysiological doses of 17β-estradiol suppress mRNA levels of MMP-3 and -13 significantly in articular chondrocytes of female patients. A significant suppressing effect was also seen in MMP-1 mRNA after a high dose of 10(-5)M 17β-estradiol. Furthermore, high doses of this hormone led to tendentially lower TIMP-1 levels whereas the TIMP-2 mRNA level was not influenced. In male patients, only incubations with high doses (10(-5)M) of 17β-estradiol were followed by a tendency to suppressed MMP-1 and TIMP-1 levels while TIMP-2 mRNA level was decreased significantly. There was no effect on MMP-13 expression of cells from male patients. Taken together, application of 17β-estradiol in physiological doses will improve the imbalance between the amounts of MMPs and TIMPs in articular chondrocytes from female patients. Downregulation of TIMP-2 by 17β-estradiol in male patients would not be articular cartilage protective.

T-2 Toxin Alters the Levels of Collagen II and Its Regulatory Enzymes MMPs/TIMP-1 in a Low-Selenium Rat Model of Kashin-Beck Disease

“…c TIMP-1, I, normal group; II, low-selenium group; III, normal + low T-2 group; IV, low selenium + low T-2 group expression of collagen II at the protein and gene levels was significantly reduced in the low Se and T-2 toxin intervention group, with the low-Se diet + high T-2 toxin subgroup showing the most obvious reduction; however, no significant difference was observed between acute (30 days) and chronic (90 days) phases in the various subgroups studied. The results corroborated previous findings [14] demonstrating significantly decreased collagen II expression by human chondrocytes from KBD patients in vitro. The damage to cartilage was generated and lesions occurred for acute poisoning, with 30-day exposure.…”

“…MMP-3 cannot directly degrade collagen II; it only degrades collagen II through MMP-1 activation [14]. MMP-13 degrades collagen I, II, III, IV, and X and is the most effective collagen II degrading enzyme, tenfold the activity of MMP-1.…”

Asian Elm tree inner bark prevents articular cartilage deterioration in ovariectomized obese rats with monoiodoacetate-induced osteoarthritis

“…The depth and extent of cartilage damage (A) and the quantification of the damage (B) were determined in hematoxylin-eosin stained, paraffin-embedded knee joint sections from MIA-injected rats (magnifying power synthesis of the cartilage through estrogen receptors (ER-a and ER-b). 38 However, the mechanism of how estradiol impairs MMP expressions remains controversial and has mostly been studied in cell cultures. 34,[38][39][40] The present study found that MIA injection elevated the expression of cytokines such as TNF-a, IL-1b, and IL-6 and the expression of MMP-3 and MMP-13 in the articular cartilage of OVX rats.…”

“…38 However, the mechanism of how estradiol impairs MMP expressions remains controversial and has mostly been studied in cell cultures. 34,[38][39][40] The present study found that MIA injection elevated the expression of cytokines such as TNF-a, IL-1b, and IL-6 and the expression of MMP-3 and MMP-13 in the articular cartilage of OVX rats. However, although 17b-estradiol treatment modulates the increased expression of MMP-3, MMP-13, and IL-1b, it did not decrease the expression of TNF-a, IL-1b, and IL-6 in the articular cartilage.…”

Royal Jelly Increases Collagen Production in Rat Skin After Ovariectomy

“…15,16 Although ERT has been used for many years, recent trials have reported significantly increased risks of breast cancer and other pathologies with this treatment. 17 Many studies are being performed to discover effective and nontoxic materials with estrogen-like activity to replace estrogen in therapies for postmenopausal women.…”