Molecules responsible for degradation of cartilage
The primary enzymes responsible for the degradation of
cartilage are the matrix metalloproteinases (MMPs). These enzymes are secreted
by both synovial cells and chondrocytes and are categorized into three general
categories: a) collagenases; b) stromelysins; and, c) gelatinases.
Factors responsible for mmps synthesis
Interleukin-1 (IL-1). IL-1 is a potent
pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial
cells to synthesize. IL-1 was known under several other names including
endogenous pyrogen, lymphocyte activating factor, haemopoetin-1 and mononuclear
cell factor, amongst others.
The Interleukin-1 super family
The original members of the IL-1 superfamily are IL-1α,
IL-1β, and the IL-1 Receptor antagonist (IL-1RA).IL-1α and -β are
pro-inflammatory cytokines involved in immune defense against infection. IL-1α
and IL-1β are produced as precursor peptides. In other words they are made as a
long protein that is then processed to release a shorter, active molecule,
which is called the mature protein.
IL-1α is a pleiotropic cytokine involved
in various immune responses, inflammatory processes, and hematopoiesis. This
cytokine is produced by many cell types but is only secreted by monocytes and macrophages.
It is produced as a proprotein, which is proteolytically processed by calpain
and released in a mechanism that is still not well studied. This gene and eight
other interleukin 1 family genes form a cytokine gene cluster on chromosome 2.
Interleukin 1, beta, also known as IL1B,
is a human gene. Interleukin-1 beta is a cytokine. IL-1β precursor is cleaved
by caspase 1 (interleukin 1 beta convertase). Cytosolic thiol protease cleaves
the product to form mature IL-1β. The protein encoded by this gene is a member
of the interleukin 1 cytokine family. This cytokine is produced by activated
macrophages as a proprotein, which is proteolytically processed to its active
form by caspase 1 (CASP1/ICE).
The IL-1RA is a molecule that competes
for receptor binding with IL-1α and IL-1β, blocking their role in immune
(IL-1R) is a cytokine receptor which binds interleukin 1. Two forms of the
- Interleukin 1 receptor, type I: The
type I receptor is primarily responsible for transmitting the inflammatory
effects of interleukin-1 (IL-1) while type II receptors may act as a
suppressor of IL-1 activity by competing for IL-1 binding.
- Interleukin 1 receptor, type II: Interleukin 1 receptor, type II (IL1R2) also known as CD121b (Cluster of Differentiation
121b) is an interleukin
receptor. IL1R2 also denotes its human gene.The protein encoded by this
gene is a cytokine receptor that belongs to the interleukin-1 receptor
family. This protein binds interleukin alpha (IL1A), interleukin beta
(IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a
decoy receptor that inhibits the activity of its ligands.
is mainly caused due to binding of IL-1 alpha with IL-1 type1 receptors. So the
structural and sequence information of them is studied in order to find the
binding sites of IL-1 type 1 receptor