MATRIX EXPRESSION IN PASSAGED CHONDROCYTES IS REGULATED BY TROPOMYOSIN 3.1
Date
2023-05
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
Cartilage is an avascular tissue that allows frictionless mobility of joints.
Cartilage cells (chondrocytes) reside in a matrix of collagens (type II collagen
[Col2]) and proteoglycans (aggrecan [Acan]) to bear mechanical load [2, 10, 14].
Unfortunately, cartilage is incapable of self-repair and damage leads to cartilage
degradation in osteoarthritis (OA).
Autologous chondrocyte implantation (ACI) is used to treat small, focal
cartilage defects. Chondrocytes are isolated from healthy regions of cartilage in
damaged joints, expanded on stiff polystyrene to increase number, then reimplanted
into damaged regions to stimulate repair. Unfortunately, ACI ultimately fails [9, 18,
20, 23]. During expansion, chondrocytes become larger, elongated, and express
fibroblastic matrix (type I collagen [Col1]) and contractile (transgelin [Tagln])
molecules, which are biomechanically inferior [2, 14, 22, 23, 39, 41, 43].
Additionally, cellular filamentous (F-)actin organization changes from cortical F actin to F-actin stress fibers. Our previous research indicates formation of F-actin
stress fibers plays a key role in chondrocyte dedifferentiation [1]. In the present
study, we examined ways to repress F-actin stress fiber formation by examining
master regulators of actin networks, the Tropomyosins (Tpm), which bind and
stabilize specific F-actinnetworks [32, 41]. Therefore, we hypothesize that
targeting specific stress fiber actin stabilizing Tpms will repress F-actin stress
fiber networks and promote chondrogenic redifferentiation after expansion.