Abstract
Human collagenase-3 expression, previously seen only in a breast tumor tissue, is here shown to be expressed in primary human chondrocytes derived from the joint tissue and in transformed human chondrocytes. Its mRNA is inducible by the inflammatory cytokines interleukin-1beta plus tumor necrosis factor-alpha, but not by phorbol 12-myristate 13-acetate and only slightly by the growth factors platelet-derived growth factor and epidermal growth factor. Human synovial fibroblasts, another prominent cell type in the joint tissue, do not produce collagenase-3 message. Expression of the murine collagenase, which is possibly the counterpart of human collagenase-3, is induced by interleukin-1beta plus tumor necrosis factor-alpha, and its full induction requires the presence of the transcription factor, c-FOS. This family of transcription factors also plays a role in induction of human collagenase-3, since it binds to the AP-1 site of this matrix metalloproteinase.
Highlights
The matrix metalloproteinases (MMPs)1 are a family of related enzymes that degrade the extracellular matrix
Expression of COL-3 in Human Chondrocytes—Many MMP genes are induced by inflammatory cytokines, growth factors, and the tumor promoter PMA, and here their effect on the recently cloned human COL-3 [8] was tested
High levels of COL-1 are expressed by cells present in the human knee joint tissue; we chose to examine two different types of primary cells obtained from this source: i.e. chondrocytes, that are responsible for maintaining cartilage-specific matrix phenotype in normal joints, and synovial fibroblasts, cells lining the synovium of the joint
Summary
The matrix metalloproteinases (MMPs) are a family of related enzymes that degrade the extracellular matrix These enzymes operate during normal development in tissue differentiation and remodeling, but are active under pathological conditions to cause inflammatory disease, degradation of bone and cartilage, as well as tumor metastasis [1,2,3]. They are secreted as inactive latent forms, depend upon a zinc-binding active site, and are inhibited by chelating agents [4] and by specific proteins referred to as the tissue inhibitors of matrix metalloproteinases or TIMPs [5]. Results from our gel supershift experiments further indicate that the AP-1 site of human COL-3 is recognized by the FOS family of proteins including FRA-1, another member of the c-FOS family of transcription factors
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