title: Phenotypic modulation of human articular chondrocytes by bistratene A.
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 (PKCdelta) 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 PKCdelta to the nuclear membrane. Concurrent treatments of chondrocytes with a specific inhibitor of PKCdelta, rottlerin, partially blocked the morphological effects of bistratene A.
authors.affiliation: Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: Gargiulo
authors.forename: P
authors.initials: P
authors.lastname: Cragg
authors.forename: J B
authors.initials: JB
authors.lastname: Richardson
authors.forename: B A
authors.initials: BA
authors.lastname: Ashton
authors.forename: W E
authors.initials: WE
authors.lastname: Johnson