Abstract
Glycosphingolipids are known to play a role in developing and maintaining the integrity of various organs and tissues. Among glycosphingolipids, there are several reports on the involvement of gangliosides in bone metabolism. However, there have been no reports on the presence or absence of expression of globo-series glycosphingolipids in osteoblasts and osteoclasts, and the involvement of their glycosphingolipids in bone metabolism. In the present study, we investigated the presence or absence of globo-series glycosphingolipids such as Gb3 (globotriaosylceramide), Gb4 (globoside), and Gb5 (galactosyl globoside) in osteoblasts and osteoclasts, and the effects of genetic deletion of Gb3 synthase, which initiates the synthesis of globo-series glycosphingolipids on bone metabolism. Among Gb3, Gb4, and Gb5, only Gb4 was expressed in osteoblasts. However, these glycosphingolipids were not expressed in pre-osteoclasts and osteoclasts. Three-dimensional micro-computed tomography (3D-μCT) analysis revealed that femoral cancellous bone mass in Gb3 synthase-knockout (Gb3S KO) mice was lower than that in wild type (WT) mice. Calcein double labeling also revealed that bone formation in Gb3S KO mice was significantly lower than that in WT mice. Consistent with these results, the deficiency of Gb3 synthase in mice decreased the number of osteoblasts on the bone surface, and suppressed mRNA levels of osteogenic differentiation markers. On the other hand, osteoclast numbers on the bone surface and mRNA levels of osteoclast differentiation markers in Gb3S KO mice did not differ from WT mice. This study demonstrated that deletion of Gb3 synthase in mice decreases bone mass via attenuation of bone formation.
Highlights
Glycosphingolipids are considered to play an important role in the development and maintenance of various organs and tissues [1,2,3]
Wfoermreaptoiornt,hleeardeinthgattoddeelcerteiaosnedobf oGnbe3msaysns.thTahsisesitnudmyiicsethresfuirlsttstoinrespigonrtifithcaatnGt ba4ttiesneuxaptrieosnsedofinbone formaotisoteno,blleaasdtsi,nagndtoaldsoectrheaatsgelodbboo‐snereiems agslysc.oTsphhisinsgtouldipyidis athreeifinvrsotlvteodrienpboornt ethmaettGabbo4lisims e. xpressed in osteoblasts, and that globo-series glycosphingolipids are involved in bone metabolism
MRNA levels of runt‐related transcription factor 2 (Runx2), alkaline phosphatase (Alp), and osteocalcin were suppressed in Gb3 synthase-knockout (Gb3S KO) mice (Figure 7)
Summary
Glycosphingolipids are considered to play an important role in the development and maintenance of various organs and tissues [1,2,3]. These have been shown to be critical for protection against. InRvoelcveendtliyn, bwoneedmemetaobnosltisrmate[5d–9t]h.aFtoar ilnasctakncoef, Git Dw3assryenptohratesde,thwathaic‐h is responsesribielsegfaonrgtlhioesigdeenGeDra1taioanndoGf Mal1l bp-rsoemrioetse ogsatneogblliaosstiidc edsif,fienremntiiacteiornesouf lbtosnienmthaerraotwtemnuesaetniochnyomfabl one loss wsittehmacgeilnlsg(M[9S].CHs)oawndevteenrd, othnesrteemhacvelelsb[e5–e8n].nRoecreenptolyr,tswoendetmheonpsrtersaetendcethoatraalbasceknocfeGoDf3esxypnrtehsassieo,n of globo-wosfehrbiicoehns eigsllryoecssospsowpnihsthiibnlagegofiloniprgitdh[9es].ginHenooeswrtaeetoviobenlra,ostfthsaealrlenbdh‐saoevrseiteesboegcealannsgntlsoi,oasrinedpdeostr,htisenormonliecthes eorefpsturhelestsesenincgetlhyoecroaasttbpeshneiunnacgteiooolnifpids in boneexmpreestasiboonliosfmg.lobo‐series glycosphingolipids in osteoblasts and osteoclasts, and the roles of these. CTtehriizsegdlyacsotshpehPiknagnotliigpeindohnarseadlsboloboedecnelrlesc[o1g4]naizneddisascoanrseidceerpetdortofobre vaetruomtooxrinanstsigeecnreted of Burkitt lymphoma [10]. This glycosphingolipid has been recognized as a receptor for by patvheorgoetonxicinEsscshecerreicthedia cboylipOa1th5o7g[e1n5i]c. Wfoermreaptoiornt,hleeardeinthgattoddeelcerteiaosnedobf oGnbe3msaysns.thTahsisesitnudmyiicsethresfuirlsttstoinrespigonrtifithcaatnGt ba4ttiesneuxaptrieosnsedofinbone formaotisoteno,blleaasdtsi,nagndtoaldsoectrheaatsgelodbboo‐snereiems agslysc.oTsphhisinsgtouldipyidis athreeifinvrsotlvteodrienpboornt ethmaettGabbo4lisims e. xpressed in osteoblasts, and that globo-series glycosphingolipids are involved in bone metabolism
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