2002   Volume No 3 - pages 9-18

Title: Phenotypic modulation of human articular chondrocytes by bistratene A

Authors: B.J. Gargiulo, P. Cragg, J.B. Richardson, B.A. Ashton and W.E.B. Johnson

Address: Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, U.K.

E-mail: w.e.b.johnson@keele.ac.uk

Key Words: Bistratene A, protein kinase C, articular chondrocyte, cell shape and differentiation.

Publication date: 25th June 2002

Abstract: Chondrocytes undergo phenotypic alterations following extended periods in monolayer culture, i.e., they become bipolar and flattened, proliferate, and synthesise type I as opposed to type II collagen. This process has been termed chondrocyte dedifferentiation. Bistratene A is a macrolide polyether that specifically activates the delta isoform of protein kinase C (PKCd) in some cell types. Here, we show that dedifferentiated human articular chondrocytes became rounded and underwent cell growth arrest after treatment with bistratene A. In addition, bistratene A-treated chondrocytes became more immunopositive for type II collagen, but less immunopositive for type I collagen. These phenotypic changes were associated with a prior and extensive disruption of actin microfilaments and translocation of PKCd to the nuclear membrane. Concurrent treatments of chondrocytes with a specific inhibitor of PKCd, rottlerin, partially blocked the morphological effects of bistratene A.

Article download: Pages 9-18 (PDF file)