Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.1.3 (
ATPase
)
65,361
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chondrocyte hypertrophy makes important contributions to bone development and growth. We have investigated a number of novel cartilage genes identified in a recent transcriptomic study to determine whether they are differentially expressed between different zones of equine foetal growth cartilage. Twelve genes (
ATP6V0D2
,
BAK1
,
DDX5
,
GNB1
,
PIP4K2A
,
RAP1B
,
RPS7
,
SRSF3
,
SUB1
,
TMSB4
,
TPI1
and
WSB2
) were found to be more highly expressed in the zone of hypertrophic chondrocytes than in the reserve or proliferative zones, whereas
FOXA3
and
SERPINA1
were expressed at lower levels in the hypertrophic zone than in the reserve zone.
ATP6V0D2
, which encodes vacuolar H
+
ATPase
(V-ATPase) V
0
subunit d
2
(ATP6V0D2), was selected for further study. Immunohistochemical analysis of ATP6V0D2 in growth cartilage showed stronger staining in hypertrophic than in reserve zone or proliferative chondrocytes. Expression of ATP6V0D2 mRNA and protein was up-regulated in the mouse chondrocytic ATDC5 cell line by conditions inducing expression of hypertrophy-associated genes including
Col10a1
and
Mmp13
(differentiation medium). In ATDC5 cells cultured in control medium, knockdown of
Atp6v0d2
or inhibition of V-
ATPase
activity using bafilomycin A1 caused a decrease in
Col2a1
expression, and in cells cultured in differentiation medium the two treatments caused a decrease in nuclear area. Inhibition of V-
ATPase
, but not
Atp6v0d2
knockdown, prevented the upregulation of
Col10a1
,
Mmp13
and
Vegf
by differentiation medium, while
Atp6v0d2
knockdown, but not inhibition of V-
ATPase
, caused an increase in the number of ATDC5 cells cultured in differentiation medium. These observations identify ATP6V0D2 as a novel chondrocyte hypertrophy-associated gene. The results are consistent with roles for V-
ATPase
, both ATP6V0D2-dependent and -independent, in supporting chondrocyte differentiation and hypertrophy.
...
PMID:The vacuolar H
+
ATPase V
0
subunit d
2
is associated with chondrocyte hypertrophy and supports chondrocyte differentiation. 2906 63