ABSTRACT
AIM:To determine the expression patterns of bone morphogenetic protein(BMP)signaling com-ponents in the mammary glands with hyperplasia(MGH)and the activation of this signaling pathway.METHODS: The female C57BL/C mice(8-weeks-old)were randomly divided into control group and hormone group with 15 mice in each group.The mice in control group were treated with PBS,while the mice in hormone group were intragastric administration with estradiol valerate(2.5 mg/kg)for 25 d,followed by progesterone(4 mg/kg)peritoneal injection for 5 d.At the end of treatments,the mammary glands were collected to determine the morphological changes, the mRNA expression of BMP signaling components and the phosphorylation level of Smad 1/5/9.RESULTS:In MGH,a part of BMP signaling pathway molecules were differentially expressed(P<0.05),including BMP ligands BMP2,4,5,6,7,9,13 and 14, BMP re-ceptor BMPR1A, and antagonists Chrdl1 and Twsg, whereas the expression levels of some molecules, such as BMP3, BMP12,BMPR1B,BMPR2,Chrd,Chrdl2 and Noggin, were not altered.The phosphorylation levels of Smad 1/5/9 was up-regulated in MGH(P<0.05).CONCLUSION: BMP signaling pathway is activated in MGH through the abnormal expression of its components.BMP signaling pathway may be a new target for MGH therapy.
ABSTRACT
Objective To analyze the effect of Noggin silencing on the BMP and Wnt signaling pathways in hair follicle development.Methods The expression of BMP-2, BMP-4, BMPR-IA, BMP-6, BMP-7, LEF-1 andβ-catenin in Noggin silencing MC3T3-E1 stable cell line was detected by RT-PCR and western blot.Results RT-PCR results showed that the expressions of five genes in BMP signaling pathway were all significantly influenced by Noggin silencing, the ex-pressions of BMP-2 (P<0.001), BMP-4 (P<0.01), BMP-6 (P<0.001) and BMP-7 (P<0.001) were all increased and the expression of BMPR-IA (P<0.01) was decreased.While the expressions of the two genes LEF-1 (P<0.001) and β-catenin ( P<0.001) in Wnt signaling pathway were significantly decreased.Western blot results showed that the ex-pressions of these proteins in the two signaling pathways were also affected.The expressions of BMP-2 (P<0.05), BMP-4 (P<0.05), BMP-6 (P<0.05) and BMP-7 (P<0.05) were all increased, while the expressions of BMPR-IA (P<0.05), LEF-1 (P<0.01) andβ-catenin (P<0.001) were decreased.Conclusions There may be a negative feedback regulation of Noggin on the BMP signaling pathway in vitro, but a positive feedback regulation on the Wnt signaling pathway in vitro.It provides certain evidence for studies on the effect of Noggin gene on BMP and Wnt signaling pathways in vivo. There may be an interaction between hair follicle development-related signaling pathways, which still needs further experi-ments to prove.
ABSTRACT
The isoflavone calycosin-7-O-β-d-glucopyranoside (CG) is a principal constituent of Astragalus membranaceus (AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin (Ocal) mRNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2 (BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family (WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.
ABSTRACT
Osteoporosis (OP) is one of the bone metabolic diseases which seriously harms the health and lives of people. The main cause of OP is that the balance between bone formation and bone absorption, i.e. the balance of the bone remodeling process,is no longer exist. When the bone absorption dominates the process, it will lead to osteopenia, destruction of bone microstructure and increased rate of fracture. Previous studies have shown that casein kinase 2-interacting protein-1 (CKIP-1) plays an important role in the process of bone tissue proliferation and differentiation. It mainly interacts with Smad ubiquitination regulatory factor 1 (Smurf 1) to affect bone metabolism. This review analyzes and summarizes the impact of CKIP-1 on bone tissue osteogenic differentiation direction and its mechanism, which may provide new idea and research orientation for future clinical treatment of osteoporosis.