The transcription factor PRDM5 is involved in endochondral bone formation by regulating collagen I in vivo

Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S110
Author(s):  
G.G. Galli ◽  
K.H. de Lichtenberg ◽  
M. Wuelling ◽  
R. Calogero ◽  
A.H. Lund
Keyword(s):  
Transcription Factor ◽  
Bone Formation ◽  
Collagen I ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

scholarly journals Smoc1 and Smoc2 regulate bone formation as downstream molecules of Runx2

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yoshifumi Takahata ◽  
Hiromasa Hagino ◽  
Ayaka Kimura ◽  
Mitsuki Urushizaki ◽  
Sachi Kobayashi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Formation ◽  
Rna Sequencing ◽  
Late Stage ◽  
Bone Sialoprotein ◽  
Endochondral Bone Formation ◽  
Endochondral Bone ◽  
Novel Targets ◽  
Essential Transcription Factor

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.

Effects of in vitro chondrogenic priming time of bone-marrow-derived mesenchymal stromal cells on in vivo endochondral bone formation

2015 ◽  
Vol 13 ◽  
pp. 254-265 ◽  
Author(s):  
Wanxun Yang ◽  
Sanne K. Both ◽  
Gerjo J.V.M. van Osch ◽  
Yining Wang ◽  
John A. Jansen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

scholarly journals In Vitro and in Vivo Endochondral Bone Formation Models Allow Identification of Anti-Angiogenic Compounds

2003 ◽  
Vol 163 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Gabri van der Pluijm ◽  
Martine Deckers ◽  
Bianca Sijmons ◽  
Henny de Groot ◽  
John Bird ◽  
...  
Keyword(s):  
Bone Formation ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

scholarly journals A Transgenic Rat for Noninvasive Assessment of Chondrogenesis in Vivo

Cartilage ◽  
2021 ◽  
pp. 194760352110572
Author(s):  
Elisabeth Ferreira ◽  
Landon B. Gatrell ◽  
Luke Childress ◽  
Hong Wu ◽  
Ryan M. Porter
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Ex Vivo ◽  
Firefly Luciferase ◽  
Bone Morphogenetic Protein 2 ◽  
Endochondral Bone Formation ◽  
Transgenic Rat ◽  
Regulatory Sequences ◽  
Endochondral Bone

Objective To support the preclinical evaluation of therapeutics that target chondrogenesis, our goal was to generate a rat strain that can noninvasively report endogenous chondrogenic activity. Design A transgene was constructed in which the dual expression of bioluminescent (firefly luciferase) and fluorescent (mCherry) reporters is controlled by regulatory sequences from rat Col2a1. Candidate lines were established on a Lewis background and characterized by serial bioluminescence imaging as well as ex vivo measurement of molecular reporter levels in several tissues. The sensitivity and specificity of the reporter strain were assessed in models of orthotopic and ectopic chondrogenesis. Results Substantial bioluminescence signal was detected from cartilaginous regions, including the appendicular synovial joints, spine, sternum, nose, and pinnae. Bioluminescent radiance was intense at 1 month of age, rapidly declined with continued development, yet remained detectable in 2-year-old animals. Explant imaging and immunohistochemistry confirmed that both molecular reporters were localized to cartilage. Implantation of wild-type bone marrow stromal cells into osteochondral defects made in both young adult and aged reporter rats led to a time-dependent elevation of intra-articular reporter activity concurrent with cartilaginous tissue repair. To stimulate ectopic, endochondral bone formation, bone morphogenetic protein 2 was overexpressed in the gastrocnemius muscle, which led to bioluminescent signal that closely preceded heterotopic ossification. Conclusions This strain can help develop strategies to stimulate cartilage repair and endochondral bone formation or to inhibit chondrogenesis associated with heterotopic ossification.

scholarly journals Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo.

1994 ◽  
Vol 126 (6) ◽  
pp. 1595-1609 ◽  
Author(s):  
S E Gitelman ◽  
M S Kobrin ◽  
J Q Ye ◽  
A R Lopez ◽  
A Lee ◽  
...  
Keyword(s):  
Bone Formation ◽  
Tumor Cells ◽  
Cho Cells ◽  
Subcutaneous Tissue ◽  
Endochondral Bone Formation ◽  
Related Factor ◽  
Tgf Beta ◽  
Endochondral Bone ◽  
Hypertrophic Cartilage

Members of the TGF-beta superfamily appear to modulate mesenchymal differentiation, including the processes of cartilage and bone formation. Nothing is yet known about the function of the TGF-beta-related factor vgr-1, also called bone morphogenetic protein-6 (BMP-6), and only limited studies have been conducted on the most closely related factors BMP-5, osteogenic protein-1 (OP-1) or BMP-7, and OP-2. Because vgr-1 mRNA has been localized in hypertrophic cartilage, this factor may play a vital role in endochondral bone formation. We developed antibodies to vgr-1, and documented that vgr-1 protein was expressed in hypertrophic cartilage of mice. To further characterize the role of this protein in bone differentiation, we generated CHO cells that overexpressed recombinant murine vgr-1 protein. Western blot analysis documented that recombinant vgr-1 protein was secreted into the media and was proteolytically processed to yield the mature vgr-1 molecule. To assess the biological activity of recombinant vgr-1 in vivo, we introduced the vgr-1-expressing CHO cells directly into the subcutaneous tissue of athymic nude mice. CHO-vgr-1 cells produced localized tumors, and the continuous secretion of vgr-1 resulted in tumors with a strikingly different gross and histological appearance as compared to the parental CHO cells. The tumors of control CHO cells were hemorrhagic, necrotic, and friable, whereas the CHO-vgr-1 tumors were dense, firm, and fibrotic. In contrast with control CHO tumors, the nests of CHO-vgr-1 tumor cells were surrounded by extensive connective tissue, which contained large regions of cartilage and bone. Further analysis indicated that secretion of vgr-1 from the transfected CHO tumor cells induced the surrounding host mesenchymal cells to develop along the endochondral bone pathway. These findings suggest that endochondral bone formation.

scholarly journals Bone Marrow Mesenchymal Stem Cells Form Ectopic Woven Bone In Vivo Through Endochondral Bone Formation

2009 ◽  
Vol 33 (4) ◽  
pp. 301-308 ◽  
Author(s):  
Sophia Chia-Ning Chang ◽  
Ching-Lung Tai ◽  
Hui-Ying Chung ◽  
Tsung-Min Lin ◽  
Long-Bin Jeng
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Endochondral Bone Formation ◽  
Endochondral Bone ◽  
Woven Bone ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Smoc1 and Smoc2 regulate bone formation as novel downstream molecules of Runx2

2021 ◽  
Author(s):  
Yoshifumi Takahata ◽  
Hiromasa Hagino ◽  
Ayaka Kimura ◽  
Mitsuki Urushizaki ◽  
Sachi Kobayashi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Formation ◽  
Rna Sequencing ◽  
Late Stage ◽  
Bone Sialoprotein ◽  
Endochondral Bone Formation ◽  
Endochondral Bone ◽  
Novel Targets ◽  
Essential Transcription Factor

Abstract Runx2 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.

A novel in vivo model to study endochondral bone formation; HIF-1α activation and BMP expression

Bone ◽  
2007 ◽  
Vol 40 (2) ◽  
pp. 409-418 ◽  
Author(s):  
Pieter J. Emans ◽  
Frank Spaapen ◽  
Don A.M. Surtel ◽  
Keryn M. Reilly ◽  
Andy Cremers ◽  
...  
Keyword(s):  
Bone Formation ◽  
In Vivo Model ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

scholarly journals Parathyroid Hormone–related Peptide (PTHrP)-dependent and -independent Effects of Transforming Growth Factor β (TGF-β) on Endochondral Bone Formation

1999 ◽  
Vol 145 (4) ◽  
pp. 783-794 ◽  
Author(s):  
Rosa Serra ◽  
Andrew Karaplis ◽  
Philip Sohn
Keyword(s):  
Bone Formation ◽  
Transforming Growth Factor ◽  
Terminal Differentiation ◽  
Transforming Growth Factor Β ◽  
Endochondral Bone Formation ◽  
Endochondral Bone ◽  
Matrix Mineralization ◽  
Parathyroid Hormone Related Peptide ◽  
Independent Effects

Previously, we showed that expression of a dominant-negative form of the transforming growth factor β (TGF-β) type II receptor in skeletal tissue resulted in increased hypertrophic differentiation in growth plate and articular chondrocytes, suggesting a role for TGF-β in limiting terminal differentiation in vivo. Parathyroid hormone–related peptide (PTHrP) has also been demonstrated to regulate chondrocyte differentiation in vivo. Mice with targeted deletion of the PTHrP gene demonstrate increased endochondral bone formation, and misexpression of PTHrP in cartilage results in delayed bone formation due to slowed conversion of proliferative chondrocytes into hypertrophic chondrocytes. Since the development of skeletal elements requires the coordination of signals from several sources, this report tests the hypothesis that TGF-β and PTHrP act in a common signal cascade to regulate endochondral bone formation. Mouse embryonic metatarsal bone rudiments grown in organ culture were used to demonstrate that TGF-β inhibits several stages of endochondral bone formation, including chondrocyte proliferation, hypertrophic differentiation, and matrix mineralization. Treatment with TGF-β1 also stimulated the expression of PTHrP mRNA. PTHrP added to cultures inhibited hypertrophic differentiation and matrix mineralization but did not affect cell proliferation. Furthermore, terminal differentiation was not inhibited by TGF-β in metatarsal rudiments from PTHrP-null embryos; however, growth and matrix mineralization were still inhibited. The data support the model that TGF-β acts upstream of PTHrP to regulate the rate of hypertrophic differentiation and suggest that TGF-β has both PTHrP-dependent and PTHrP-independent effects on endochondral bone formation.

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