LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.
In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.
Gong
Y
Y
Slee
R B
RB
Fukai
N
N
Rawadi
G
G
Roman-Roman
S
S
Reginato
A M
AM
Wang
H
H
Cundy
T
T
Glorieux
F H
FH
Lev
D
D
Zacharin
M
M
Oexle
K
K
Marcelino
J
J
Suwairi
W
W
Heeger
S
S
Sabatakos
G
G
Apte
S
S
Adkins
W N
WN
Allgrove
J
J
Arslan-Kirchner
M
M
Batch
J A
JA
Beighton
P
P
Black
G C
GC
Boles
R G
RG
Boon
L M
LM
Borrone
C
C
Brunner
H G
HG
Carle
G F
GF
Dallapiccola
B
B
De Paepe
A
A
Floege
B
B
Halfhide
M L
ML
Hall
B
B
Hennekam
R C
RC
Hirose
T
T
Jans
A
A
Jüppner
H
H
Kim
C A
CA
Keppler-Noreuil
K
K
Kohlschuetter
A
A
LaCombe
D
D
Lambert
M
M
Lemyre
E
E
Letteboer
T
T
Peltonen
L
L
Ramesar
R S
RS
Romanengo
M
M
Somer
H
H
Steichen-Gersdorf
E
E
Steinmann
B
B
Sullivan
B
B
Superti-Furga
A
A
Swoboda
W
W
van den Boogaard
M J
MJ
Van Hul
W
W
Vikkula
M
M
Votruba
M
M
Zabel
B
B
Garcia
T
T
Baron
R
R
Olsen
B R
BR
Warman
M L
ML
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000818:Animals; D021461:Animals, Outbred Strains; D015519:Bone Density / Q000235:genetics*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D000072261:Dishevelled Proteins; D005123:Eye / Q000196:embryology*; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000378:metabolism*; D010024:Osteoporosis / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D011994:Recombinant Proteins; D015398:Signal Transduction; D012886:Skull / Q000166:cytology; D013045:Species Specificity; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D013577:Syndrome; D014162:Transfection; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051154:Wnt2 Protein; D060508:Wnt3 Protein; D060528:Wnt4 Protein; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D000072261:Dishevelled Proteins; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C555581:WNT4 protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051154:Wnt2 Protein; D060508:Wnt3 Protein; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D029961:Zebrafish Proteins; C499469:recombinant human bone morphogenetic protein-2