Search Results
tissue inhibitor matrix metalloproteinases (TIMPs) in tendon-derived cells, which are vital for tendon ECM remodeling. In the context of equine DDFT injuries, determining the biological mechanisms controlling macrophages and DDF tenocytes may shed light
, 14 , 15 Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to play a pivotal role in this process, with measurable concentrations of MMPs and TIMPs in the tissues of the trabecular meshwork and aqueous
maladaptive cardiac remodeling is the hallmark of DCM. 2,3 Matrix metalloproteinases, zinc-dependent ECM-degrading endopeptidases, and TIMPs are important regulators of tissue remodeling. 2,3,6 Various MMPs are reportedly involved in cardiac remodeling
IL-1β–stimulated NO production 24 and has proven beneficial for matrix protection because it modulates secretion of TIMPs 25 and decreases the synthesis of MMPs. 26,27 On the other hand, TGF-β has a number of effects that promote cartilage
and, at the same time, decreasing the production of TIMPs. 1–5 The inducible enzyme responsible for nitric oxide production (ie, iNOS) and enzymes that catalyze the formation of PGE 2 (ie, COX-2 and mPGEs1) are increased in articular cartilage
concentration, 18 but expression of MMPs and TIMPs in cats with renal disease has not been characterized. Vascular endothelial growth factor, a proliferative, survival, and trophic factor for endothelial cells, is also strongly stimulated by hypoxia 19
II), proteinases (MMP-2, MMP-3, MMP-9, MMP-13, ADAMTS-4 [also called aggrecanase-1], and ADAMTS-5 [also called aggrecanase-2]), proteinase inhibitors (TIMP-1, TIMP-2, and TIMP-3), inflammatory indicators (IL-1β, tumor necrosis factor-α, COX-1, COX-2
Scientific). Based on proteomic results, gene expression of insulin-like growth factor-binding protein 2 ( IGFBP2 ), metalloproteinase inhibitor 3 precursor ( TIMP3 ), and tumor necrosis factor receptor superfamily member 11B ( TNFRSF11B ) were quantified by
, MMP-2 , MMP-7 , MMP-9 , and TIMP-1 ) and downregulation of VEGFA that persisted for 6 months following the ischemic episode. 20 A subsequent study 21 of cats with naturally occurring CKD shows similar patterns of differential regulation
Abstract
Objective—To elucidate tissue inhibitor of metalloproteinase (TIMP)-mediated effects on chondrocytes.
Sample Population—Articular cartilage from humeral heads of 6 dogs.
Procedure—Chondrocytes from harvested specimens were cultured in 3-dimensional (3-D) agarose at 106 cells/mL. We prepared 3-D constructs exposed to only tumor necrosis factor (TNF)-α (50 ng/mL). Recombinant human TIMP-1 (255nM), -2 (285nM), or -3 (250nM) was added to liquid media bathing 3-D constructs cultured with TNF-α. Chondrocytes cultured without TIMP or TNF-α served as control samples. Samples of liquid media were collected on days 6, 9, 15, and 21 of culture for evaluation of glycosaminoglycan (GAG) and nitric oxide concentrations. The 3-D constructs were collected on days 9, 15, and 21 for evaluation of GAG, hydroxyproline (HP), and DNA contents.
Results—GAG content in control samples increased significantly during the study, whereas GAG content in 3-D constructs cultured with TNF-α or TNF-α plus TIMP did not increase. On day 9, GAG release from 3-D constructs cultured with TNF-α was significantly higher than that in other constructs. The HP content in control samples increased during the study and was significantly higher than that in all other constructs on day 21. Concentrations of nitric oxide were significantly lower in control samples on day 6, compared with concentrations for all other constructs.
Conclusions and Clinical Relevance—Addition of TIMPs did not counteract suppression of GAG and HP accumulation in 3-D constructs exposed to TNF-α. Apparently, adverse effects on chondrocytes exposed to TNF-α cannot be prevented by addition of TIMP alone. (Am J Vet Res 2004;65:1611–1615)
