title: TGF-beta2 prevents the impaired chondrocyte proliferation induced by unloading in growth plates of young rats.
abstract: Growth plate width and cartilage organization are altered during skeletal unloading in growing rats. Immunohistochemical studies have identified TGF-beta in calcified cartilage, and TGF-beta is known to induce mitogenic effects on chondrocytes in vitro. On the other hand, IGF-1 was shown to be expressed in the proximal tibial growth plate and to mediate GH-induced longitudinal bone growth in rats. We therefore investigated the effect of recombinant human (rh) IGF-1 and rhTGF-beta2 infusion on the changes induced by unloading in the cellular organization of the growth plate in growing rats. Hindlimb unloading for 14 days induced a 13% reduction in growth cartilage height in the proximal tibia. This effect was mostly related to a 17% and 14% decrease in the proliferative zone height and chondrocyte number, respectively. In unloaded rats treated with a systemic infusion of rhTGF-beta2 (2microg/kg/day) the number of chondrocytes in the proliferative zone was not different from those of normal loaded animals. In contrast, rhIGF-1 treatment at a 2mg/kg/day dose was not effective in counteracting the effects of unloading on growth plate height and chondrocyte number. These results show that systemic administration of rhTGF-beta2 prevents in large part the reduced growth of chondrocytes in the proliferative zone and the reduced epiphyseal growth plate growth induced by unloading in rats.
authors.affiliation: IMASSA-CERMA, Dept Physiologie Gravitationnelle, Brétigny, France. cerma@imassa.fr
authors.forename: E
authors.initials: E
authors.lastname: Zerath
authors.forename: X
authors.initials: X
authors.lastname: Holy
authors.forename: J M
authors.initials: JM
authors.lastname: Mouillon
authors.forename: B
authors.initials: B
authors.lastname: Farbos
authors.forename: M
authors.initials: M
authors.lastname: Machwate
authors.forename: C
authors.initials: C
authors.lastname: Andre
authors.forename: S
authors.initials: S
authors.lastname: Renault
authors.forename: P J
authors.initials: PJ
authors.lastname: Marie
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000502:physiology; D006132:Growth Plate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I