Runx1 up-regulates chondrocyte to osteoblast lineage commitment and promotes bone formation by enhancing both chondrogenesis and osteogenesis
Chen-Yi Tang,Chen-Yi Tang,Wei Chen,Yuan Luo,Yuan Luo,Jinjin Wu,Yan Zhang,Abigail McVicar,Matthew McConnell,Yuehua Liu,Hou-De Zhou,Yi-Ping Li +11 more
TLDR
It is revealed that Runt-related transcription factor 1 (Runx1) signals chondrocyte to osteoblast lineage commitment and promotes endochondral bone formation through enhancing both chondrogenesis and osteogenesis genes expressions, indicating Runx1 may be a therapeutic target to enhance endochondrals bone formation and prevent osteoporosis fractures.Abstract:
One of the fundamental questions in bone biology is where osteoblasts originate and how osteoblast differentiation is regulated. The mechanism underlying which factors regulate chondrocyte to osteoblast lineage commitment remains unknown. Our data showed that Runt-related transcription factor 1 (Runx1) is expressed at different stages of both chondrocyte and osteoblast differentiation. Runx1 chondrocyte-specific knockout (Runx1f/fCol2α1-cre) mice exhibited impaired cartilage formation, decreased bone density, and an osteoporotic phenotype. The expressions of chondrocyte differentiation regulation genes, including Sox9, Ihh, CyclinD1, PTH1R, and hypertrophic chondrocyte marker genes including Col2α1, Runx2, MMP13, Col10α1 in the growth plate were significantly decreased in Runx1f/fCol2α1-cre mice chondrocytes. Importantly, the expression of osteoblast differentiation regulation genes including Osx, Runx2, ATF4, and osteoblast marker genes including osteocalcin (OCN) and osteopontin (OPN) were significantly decreased in the osteoblasts of Runx1f/fCol2α1-cre mice. Notably, our data showed that osteoblast differentiation regulation genes and marker genes are also expressed in chondrocytes and the expressions of these marker genes were significantly decreased in the chondrocytes of Runx1f/fCol2α1-cre mice. Our data showed that chromatin immunoprecipitation (ChIP) and promoter mapping analysis revealed that Runx1 directly binds to the Indian hedgehog homolog (Ihh) promoter to regulate its expression, indicating that Runx1 directly regulates the transcriptional expression of chondrocyte genes. Collectively, we revealed that Runx1 signals chondrocyte to osteoblast lineage commitment and promotes endochondral bone formation through enhancing both chondrogenesis and osteogenesis genes expressions, indicating Runx1 may be a therapeutic target to enhance endochondral bone formation and prevent osteoporosis fractures.read more
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Regulation of Osteoblast Differentiation by Cytokine Networks
TL;DR: In this article, the authors review and discuss the role of cytokines in osteoblast differentiation and propose potential therapeutic targets in bone-related diseases, such as cancer, osteogenesis, and bone growth.
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Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways
Chen-Yi Tang,Chen-Yi Tang,Mengrui Wu,Mengrui Wu,Dongfeng Zhao,Dongfeng Zhao,Diep N Edwards,Abigail McVicar,Yuan Luo,Guochun Zhu,Yongjun Wang,Hou-De Zhou,Wei Chen,Yi-Ping Li +13 more
TL;DR: In this paper, the role of Runx1 in different cell populations with regards to BMP and Wnt signaling pathways and in the interacting network underlying bone homeostasis as well as adipogenesis was investigated.
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Senescent cells suppress innate smooth muscle cell repair functions in atherosclerosis.
Bennett G. Childs,Cheng Zhang,Fahad Shuja,Ines Sturmlechner,Ines Sturmlechner,Shawn Trewartha,Raul O. Fierro Velasco,Darren J. Baker,Hu Li,Jan M. van Deursen +9 more
TL;DR: The data indicate that the intermittent use of senolytic agents or IGFBP-3 inhibition in combination with lipid lowering drugs may provide therapeutic benefit in atherosclerosis.
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Aspirin modified strontium-doped β-tricalcium phosphate can accelerate the healing of femoral metaphyseal defects in ovariectomized rats.
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Simvastatin can enhance the osseointegration of titanium rods in ovariectomized rats maintenance treatment with valproic acid.
TL;DR: The present study suggests that systemic use of VPA may bring harm to the stability of titanium implants in osteoporosis, SIM can reverse the negative effect of Vpa on the osseointegration of titanium rods in ovariectomized rats.
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