scholarly journals Periostin Mediates Oestrogen-Induced Osteogenic Differentiation of Bone Marrow Stromal Cells in Ovariectomised Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Chunrong Li ◽  
Xin Li ◽  
Xian Wang ◽  
Pei Miao ◽  
Jia Liu ◽  
...  

Osteoporosis is a metabolic disease that results in the progressive loss of bone mass, which, in postmenopausal women, is related to oestrogen deficiency. Periostin (POSTN) plays a key role in the early stages of bone formation. However, whether POSTN participates in oestradiol regulation of osteogenic differentiation of bone marrow stromal cells (BMSCs) from ovariectomised (OVX) rats remains unclear. In vivo, using microcomputed tomography (micro-CT), immunohistochemistry, and dynamic analysis of femurs, we found that 17β-E2 promotes bone formation and POSTN expression at the endosteal surface. In vitro, 17β-E2 upregulated POSTN expression in OVX-BMSCs. POSTN overexpression activated the Wnt/β-catenin signalling pathway and enhanced osteogenic differentiation of OVX-BMSCs. Furthermore, knockdown of Postn blocks the involvement of 17β-E2 in the osteogenic differentiation of OVX-BMSCs. Collectively, our study indicated the role of POSTN in the osteogenesis and stemness of OVX-BMSCs and proves that 17β-E2 reduces osteoporosis and promotes osteogenesis through the POSTN-Wnt/β-catenin pathway. POSTN could, therefore, be a novel target gene for anti-osteoporosis therapies.

2005 ◽  
Vol 242 (6) ◽  
pp. 859-868 ◽  
Author(s):  
Claude Jaqui??ry ◽  
Stefan Schaeren ◽  
Jian Farhadi ◽  
Pierre Mainil-Varlet ◽  
Christoph Kunz ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5042-5042
Author(s):  
Kenji Ishitsuka ◽  
Teru Hideshima ◽  
Paola Neri ◽  
Sonia Vallet ◽  
Norihiko Shiraishi ◽  
...  

Abstract The interaction between multiple myeloma (MM) cells and the bone marrow (BM) microenvironment plays a crucial role not only in proliferation and survival of MM cells, but also in osteoclastogenesis. In this study, we examined diverse potential of novel p38MAPK inhibitor LSN2322600 (LSN) for MM therapy in vitro and in vivo. The cytotoxic activity of LSN against MM cell lines was modest; however, LSN significantly enhances the cytotoxicity of Bortezomib by down-regulating Bortezomib-induced heat shock protein (HSP) 27 phosphorylation. We next examined the effects of LSN on cytokine secretion in MM cells, bone marrow stromal cells and osteoclast precursor cells. LSN inhibited IL-6 secretion from long-term cultured-bone marrow stromal cells (LT-BMSCs) and bone marrow mononuclear cells (BMMNCs) from MM patients in remission. LSN also inhibited MIP-1 α secretion by fresh tumor cells, BMMNCs and CD14 positive cells. Since these cytokines mediate osteoclastogenesis, we further examined whether LSN could inhibit osteoclastogenesis. Importantly, LSN inhibited in vitro osteoclastogenesis induced by macrophage-colony stimulating factor (M-CSF) and soluble receptor activator of nuclear factor- κ B ligand (sRANKL), as well as osteoclastogenesis in the severe combined immunodeficiency (SCID)-Hu mouse model of human MM. These results suggest that LSN represents a promising novel targeted strategy to reduce skeletal complications as well as to sensitize or overcome resistance to Bortezomib.


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