title: Effect of porcine fetal enamel matrix derivative on chondrocyte proliferation, differentiation, and local factor production is dependent on cell maturation state.
abstract: Recent studies have shown that porcine fetal enamel matrix derivative (EMD) can enhance the osteoinductive ability of demineralized freeze-dried bone allograft (DFDBA) in a nude mouse muscle implantation model. This suggests that one or more components of EMD can regulate the process of endochondral ossification initiated by DFDBA. To substantiate this hypothesis, in the current study, chondrocytes in the endochondral pathway at two stages of maturation were tested for their response to EMD. Chondrocytes were isolated from the resting zone and growth zone (prehypertrophic and upper hypertrophic cell zones) of the costochondral growth plate cartilage of adolescent rats. The results showed that the relatively immature resting zone cells responded to EMD with an increase in proliferation and a decrease in differentiation as measured by alkaline-phosphatase-specific activity. In addition, EMD stimulated a fivefold increase in PGE(2) production, but was without effect on collagen synthesis, proteoglycan sulfation, and TGF-beta(1) production. The more mature growth zone cells also responded to EMD with increased proliferation, but alkaline-phosphatase-specific activity was unchanged, and there was only a modest increase in PGE(2) production. In contrast to resting zone cells, growth zone cells exhibited a decrease in collagen synthesis, proteoglycan sulfation, and TGF-beta(1) production. These observations indicate that EMD has prominent effects on cells in the endochondral pathway. In particular, EMD stimulates the production of more cells, but inhibits their maturation. This would increase the pool of cells available for subsequent differentiation in response to other factors.
authors.affiliation: Department of Orthopaedics, University of Texas Health Science Center, San Antonio 78229-3900, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Dean
authors.forename: C H
authors.initials: CH
authors.lastname: Lohmann
authors.forename: V L
authors.initials: VL
authors.lastname: Sylvia
authors.forename: D L
authors.initials: DL
authors.lastname: Cochran
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: B D
authors.initials: BD
authors.lastname: Boyan
authors.forename: Z
authors.initials: Z
authors.lastname: Schwartz
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000502:physiology*; D003094:Collagen / Q000096:biosynthesis; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D008297:Male; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D003746:Dental Enamel Proteins; D011509:Proteoglycans; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C109069:enamel matrix proteins; D003094:Collagen; D000469:Alkaline Phosphatase; D015232:Dinoprostone