A Role for Retinoic Acid in Regulating the Regeneration of Deer Antlers

Developmental Biology

M. Maden¹  J.S. Price¹  S.P. Allen¹ 

[1] Department of Veterinary Basic Sciences, The Royal Veterinary College, London, United Kingdom, NW1 OTU

关键词: retinoic acid;    deer antler;    cartilage;    bone;    retinoic acid receptor;    retinoid X receptor;    chondrocyte;    osteoblast;    RALDH2;   

DOI  :  10.1006/dbio.2002.0816

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Deerantlersaretheonlymammalianorgansthatcanberepeatedlyregenerated;eachyear,thesecomplexstructuresareshedandthenregrowtobeusedfordisplayandfighting.Todate,themolecularmechanismscontrollingantlerregenerationarenotwellunderstood.VitaminAanditsderivatives,retinoicacids,playimportantrolesinembryonicskeletaldevelopment.Here,weprovideseverallinesofevidenceconsistentwithretinoidsplayingafunctionalroleincontrollingcellulardifferentiationduringboneformationintheregeneratingantler.Threereceptors(α,β,γ)forboththeretinoicacidreceptor(RAR)andretinoidXreceptor(RXR)familiesshowdistinctpatternsofexpressioninthegrowingantlertip,thesiteofendochondralossification.RARαandRXRβareexpressedinskin(“velvet”)andtheunderlyingperichondrium.Incartilage,whichisvascularised,RXRβisspecificallyexpressedinchondrocytes,whichexpresstypeIIcollagen,andRARαinperivascularcells,whichalsoexpresstypeIcollagen,amarkeroftheosteoblastphenotype.High-performanceliquidchromatographyanalysisshowssignificantamountsofVitaminA(retinol)inantlertissuesatallstagesofdifferentiation.Themetabolitesall-trans-RAand4-oxo-RAarefoundinskin,perichondrium,cartilage,bone,andperiosteum.TheRXRligand,9-cis-RA,isfoundinperichondrium,mineralisedcartilage,andbone.TofurtherdefinesitesofRAsynthesisinantler,weimmunolocalisedretinaldehydedehydrogenasetype2(RALDH-2),amajorretinoicacid-generatingenzyme.RALDH-2isexpressedintheskinandperichondriumandinperivascularcellsincartilage,althoughchondroprogenitorsandchondrocytesexpressverylowlevels.Atsitesofboneformation,differentiatedosteoblastswhichexpressthebone-specificproteinosteocalcinexpresshighlevelsofRALDH2.TheeffectofRAonantlercelldifferentiationwasstudiedinvitro;all-trans-RAinhibitsexpressionofthechondrocytephenotype,aneffectthatisblockedbyadditionoftheRARantagonistRo41-5253.Inmonolayerculturesofmesenchymalprogenitorcells,all-trans-RAincreasestheexpressionofalkalinephosphatase,amarkeroftheosteoblasticphenotype.Insummary,thisstudyhasshownthatantlertissuescontainendogenousretinoids,including9-cisRA,andtheenzymeRALDH2thatgeneratesRA.SitesofRAsynthesisinantlercorrespondcloselywiththelocalisationofcellswhichexpressreceptorsfortheseligandsandwhichrespondtotheeffectsofRA.

【 授权许可】

Unknown