DEFECT IN FORMATION OF FUNCTIONAL MATRIX VESICLES BY GROWTH-PLATE CHONDROCYTES IN AVIAN TIBIAL DYSCHONDROPLASIA - EVIDENCE OF DEFECTIVE TISSUE VASCULARIZATION
Dt. Nie et al., DEFECT IN FORMATION OF FUNCTIONAL MATRIX VESICLES BY GROWTH-PLATE CHONDROCYTES IN AVIAN TIBIAL DYSCHONDROPLASIA - EVIDENCE OF DEFECTIVE TISSUE VASCULARIZATION, Journal of bone and mineral research, 10(11), 1995, pp. 1625-1634
Avian tibial dyschondroplasia (ATD), a disease characterized by an alm
ost total lack of mineralization in affected areas of growth plate car
tilage, may involve defective matrix vesicle (MV) mineralization. To e
xplore the biochemical defect in ATD, both normal and diseased tissue
were analyzed for the amount of isolatable MVs, their chemical composi
tion, and their ability to induce mineral formation. We found signific
antly fewer MVs in ATD tissue, and in contrast to normal MVs, which ra
pidly mineralized when incubated in synthetic cartilage lymph, those i
solated from ATD lesions induced only limited mineralization even afte
r prolonged incubation. Analysis by detergent extraction revealed a ne
arly dysfunctional nucleational core in ATD MVs. Thus, in ATD tissue,
there is a defect in the formation of MVs, and those that form are nea
rly inactive. There were also alterations in the lipid-dependent Ca2+-
binding proteins (annexins) in ATD MVs. There were lower levels of ann
exins II and VI in endogenously produced collagenase-released matrix v
esicles (CRMVs), but not in matrix vesicle-enriched microsomes (MVEMs)
produced by tissue homogenization. These findings indicate that there
is insufficient Ca2+ in ATD cells to enable incorporation of the anne
xins into MVs. Finally, there was evidence of phospholipid breakdown i
n ATD MVs, as well as in ATD tissue generally. This indicated that the
ATD lesions were becoming necrotic. Taken together, these findings in
dicate that there is a defect in tissue vascularization such that the
supply of mineral ions and nutrients to ATD cartilage is inadequate to
support normal MV formation and subsequent mineralization.