Impairment of medullary bone formation, resorption and response to PTH in marrow ablated bone sialoprotein (BSP) knockout mice

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S60
Author(s):  
N.M. Wade-Gueye ◽  
M. Boudiffa ◽  
A. Vanden-Bossche ◽  
F. Gueniche ◽  
N. Laroche ◽  
...  
2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yoshifumi Takahata ◽  
Hiromasa Hagino ◽  
Ayaka Kimura ◽  
Mitsuki Urushizaki ◽  
Sachi Kobayashi ◽  
...  

AbstractRunx2 is an essential transcription factor for bone formation. Although osteocalcin, osteopontin, and bone sialoprotein are well-known Runx2-regulated bone-specific genes, the skeletal phenotypes of knockout (KO) mice for these genes are marginal compared with those of Runx2 KO mice. These inconsistencies suggest that unknown Runx2-regulated genes play important roles in bone formation. To address this, we attempted to identify the Runx2 targets by performing RNA-sequencing and found Smoc1 and Smoc2 upregulation by Runx2. Smoc1 or Smoc2 knockdown inhibited osteoblastogenesis. Smoc1 KO mice displayed no fibula formation, while Smoc2 KO mice had mild craniofacial phenotypes. Surprisingly, Smoc1 and Smoc2 double KO (DKO) mice manifested no skull, shortened tibiae, and no fibulae. Endochondral bone formation was also impaired at the late stage in the DKO mice. Collectively, these results suggest that Smoc1 and Smoc2 function as novel targets for Runx2, and play important roles in intramembranous and endochondral bone formation.


2019 ◽  
Vol 50 (4) ◽  
pp. 389-404 ◽  
Author(s):  
Shinji Hiyama ◽  
Miyuki Yokoi ◽  
Yuichi Akagi ◽  
Yumiko Kadoyama ◽  
Kiichi Nakamori ◽  
...  

Bone ◽  
1985 ◽  
Vol 6 (5) ◽  
pp. 391-393 ◽  
Author(s):  
J.P. Van De Velde ◽  
J.P.W. Vermeiden ◽  
B.J. Hagen ◽  
F.C. Van Ginkel ◽  
B. Prahl-Andersen

2008 ◽  
Vol 205 (5) ◽  
pp. 1145-1153 ◽  
Author(s):  
Luc Malaval ◽  
Ndéyé Marième Wade-Guéye ◽  
Maya Boudiffa ◽  
Jia Fei ◽  
Ralph Zirngibl ◽  
...  

Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (−/−) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP−/− mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (≥12 mo) BSP−/− mice. At 4 mo, BSP−/− mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP−/− versus WT bone marrow stromal cultures. BSP−/− hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP−/− mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN−/− mice.


2009 ◽  
Vol 10 (8) ◽  
pp. 1209-1217 ◽  
Author(s):  
N. Arai ◽  
K. Ohya ◽  
S. Kasugai ◽  
H. Shimokawa ◽  
S. Ohida ◽  
...  

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Gehua Zhen ◽  
Yang Dan ◽  
Ruomei Wang ◽  
Ce Dou ◽  
Qiaoyue Guo ◽  
...  

AbstractOsteoporosis (OP) is a common age-related disease characterized by a deterioration of bone mass and structure that predisposes patients to fragility fractures. Pharmaceutical therapies that promote anabolic bone formation in OP patients and OP-induced fracture are needed. We investigated whether a neutralizing antibody against Siglec-15 can simultaneously inhibit bone resorption and stimulate bone formation. We found that the multinucleation of osteoclasts was inhibited in SIGLEC-15 conditional knockout mice and mice undergoing Siglec-15 neutralizing antibody treatment. The secretion of platelet-derived growth factor-BB (PDGF-BB), the number of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear cells, and bone formation were significantly increased in the SIGLEC-15 conditional knockout mice and antibody-treated mice. The anabolic effect of the Siglec-15 neutralizing antibody on bone formation was blunted in mice with Pdgfb deleted in TRAP+ cells. These findings showed that the anabolic effect of the Siglec-15 neutralizing antibody was mediated by elevating PDGF-BB production of TRAP+ mononuclear cells. To test the therapeutic potential of the Siglec-15 neutralizing antibody, we injected the antibody in an ovariectomy-induced osteoporotic mouse model, which mimics postmenopausal osteoporosis in women, and in two fracture healing models because fracture is the most serious health consequence of osteoporosis. The Siglec-15 neutralizing antibody effectively reduced bone resorption and stimulated bone formation in estrogen deficiency-induced osteoporosis. Of note, the Siglec-15 neutralizing antibody promoted intramembranous and endochondral ossification at the damaged area of cortical bone in fracture healing mouse models. Thus, the Siglec-15 neutralizing antibody shows significant translational potential as a novel therapy for OP and bone fracture.


2017 ◽  
Author(s):  
Natalie Butterfield ◽  
Justyna Miszkiewicz ◽  
John Logan ◽  
Victoria Leitch ◽  
Takashi Yoshimura ◽  
...  

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