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Suppression of zinc finger protein 467 alleviates osteoporosis through promoting differentiation of adipose derived stem cells to osteoblasts.

You L, Pan L, Chen L, Chen JY, Zhang X, Lv Z, Fu D - J Transl Med (2012)

Bottom Line: Our results showed that RNA interference for Zfp467 in ADSCs inhibited adipocyte formation and stimulated osteoblast commitment.The mRNA levels of osteogenic and adipogenic markers in ADSCs were regulated by si-Zfp467.Thus Zfp467 play an important role in ADSCs differentiation to adipocyte and osteoblast.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Osteoporosis, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China. youlisky2002@126.com

ABSTRACT
Osteoblast and adipocyte are derived from common mesenchymal progenitor cells. The bone loss of osteoporosis is associated with altered progenitor differentiation from an osteoblastic to an adipocytic lineage. In this study, a comparative analysis of gene expression profiling using cDNA microarray and realtime-PCR indicated that Zinc finger protein 467 (Zfp467) involved in adipocyte and osteoblast differentiation of cultured adipose derived stem cells (ADSCs). Our results showed that RNA interference for Zfp467 in ADSCs inhibited adipocyte formation and stimulated osteoblast commitment. The mRNA levels of osteogenic and adipogenic markers in ADSCs were regulated by si-Zfp467. Zfp467 RNAi in ADSCs could restore bone function and structure in an ovariectomized (OVX)-induced osteoporotic mouse model. Thus Zfp467 play an important role in ADSCs differentiation to adipocyte and osteoblast. This has relevance to therapeutic interventions in osteoporosis, including si-Zfp467-based therapies currently available, and may be of relevance for the use of adipose-derived stem cells for tissue engineering.

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The mRNA and protein levels of Zfp467 in cultured adipocyte, osteoblast and undifferentiated ADSCs. The mRNA and protein levels of Zfp467 in adipocyte and osteoblast derived from ADSCs at day 14 and undifferentiated ADSCs (Day 0) were measured using qRT-PCR (A) and Western blot analysis (B). The data are representative of three independent experiments. The two si-Zfp467 vector (pSilencer4.1-si-Zfp467 with neomycin resistance), which produces specific siRNA (Zfp467-KD1 and -KD2) were used in the experiment. Scrambled siRNA was used as a control for siRNA-Zfp467. The efficiencies of Zfp467 RNAi in ADSCs were evaluated using qRT-PCR (C) and Western blot analysis (D).
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Figure 4: The mRNA and protein levels of Zfp467 in cultured adipocyte, osteoblast and undifferentiated ADSCs. The mRNA and protein levels of Zfp467 in adipocyte and osteoblast derived from ADSCs at day 14 and undifferentiated ADSCs (Day 0) were measured using qRT-PCR (A) and Western blot analysis (B). The data are representative of three independent experiments. The two si-Zfp467 vector (pSilencer4.1-si-Zfp467 with neomycin resistance), which produces specific siRNA (Zfp467-KD1 and -KD2) were used in the experiment. Scrambled siRNA was used as a control for siRNA-Zfp467. The efficiencies of Zfp467 RNAi in ADSCs were evaluated using qRT-PCR (C) and Western blot analysis (D).

Mentions: We then choose Zfp467, a novel regulator of osteoblast and adipocyte commitment [18], to further study the molecule mechanism of ADSCs differentiation. The mRNA and protein levels of Zfp467 in adipocyte and osteoblast derived from ADSCs (Day 14) and control (ADSCs, Day 0) were measured using qRT-PCR and Western blot analysis, respectively. The results showed that the mRNA levels of Zfp467 in adipocyte derived from ADSCs was notably increased when compared with that in the control, however the mRNA levels of Zfp467 was significantly decrease after ADSCs differentiation to osteoblast (Figure 4A). The change of Zfp467 protein levels showed to be the same on the mRNA levels of Zfp467 in three groups (Figure 4B).


Suppression of zinc finger protein 467 alleviates osteoporosis through promoting differentiation of adipose derived stem cells to osteoblasts.

You L, Pan L, Chen L, Chen JY, Zhang X, Lv Z, Fu D - J Transl Med (2012)

The mRNA and protein levels of Zfp467 in cultured adipocyte, osteoblast and undifferentiated ADSCs. The mRNA and protein levels of Zfp467 in adipocyte and osteoblast derived from ADSCs at day 14 and undifferentiated ADSCs (Day 0) were measured using qRT-PCR (A) and Western blot analysis (B). The data are representative of three independent experiments. The two si-Zfp467 vector (pSilencer4.1-si-Zfp467 with neomycin resistance), which produces specific siRNA (Zfp467-KD1 and -KD2) were used in the experiment. Scrambled siRNA was used as a control for siRNA-Zfp467. The efficiencies of Zfp467 RNAi in ADSCs were evaluated using qRT-PCR (C) and Western blot analysis (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3293781&req=5

Figure 4: The mRNA and protein levels of Zfp467 in cultured adipocyte, osteoblast and undifferentiated ADSCs. The mRNA and protein levels of Zfp467 in adipocyte and osteoblast derived from ADSCs at day 14 and undifferentiated ADSCs (Day 0) were measured using qRT-PCR (A) and Western blot analysis (B). The data are representative of three independent experiments. The two si-Zfp467 vector (pSilencer4.1-si-Zfp467 with neomycin resistance), which produces specific siRNA (Zfp467-KD1 and -KD2) were used in the experiment. Scrambled siRNA was used as a control for siRNA-Zfp467. The efficiencies of Zfp467 RNAi in ADSCs were evaluated using qRT-PCR (C) and Western blot analysis (D).
Mentions: We then choose Zfp467, a novel regulator of osteoblast and adipocyte commitment [18], to further study the molecule mechanism of ADSCs differentiation. The mRNA and protein levels of Zfp467 in adipocyte and osteoblast derived from ADSCs (Day 14) and control (ADSCs, Day 0) were measured using qRT-PCR and Western blot analysis, respectively. The results showed that the mRNA levels of Zfp467 in adipocyte derived from ADSCs was notably increased when compared with that in the control, however the mRNA levels of Zfp467 was significantly decrease after ADSCs differentiation to osteoblast (Figure 4A). The change of Zfp467 protein levels showed to be the same on the mRNA levels of Zfp467 in three groups (Figure 4B).

Bottom Line: Our results showed that RNA interference for Zfp467 in ADSCs inhibited adipocyte formation and stimulated osteoblast commitment.The mRNA levels of osteogenic and adipogenic markers in ADSCs were regulated by si-Zfp467.Thus Zfp467 play an important role in ADSCs differentiation to adipocyte and osteoblast.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Osteoporosis, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China. youlisky2002@126.com

ABSTRACT
Osteoblast and adipocyte are derived from common mesenchymal progenitor cells. The bone loss of osteoporosis is associated with altered progenitor differentiation from an osteoblastic to an adipocytic lineage. In this study, a comparative analysis of gene expression profiling using cDNA microarray and realtime-PCR indicated that Zinc finger protein 467 (Zfp467) involved in adipocyte and osteoblast differentiation of cultured adipose derived stem cells (ADSCs). Our results showed that RNA interference for Zfp467 in ADSCs inhibited adipocyte formation and stimulated osteoblast commitment. The mRNA levels of osteogenic and adipogenic markers in ADSCs were regulated by si-Zfp467. Zfp467 RNAi in ADSCs could restore bone function and structure in an ovariectomized (OVX)-induced osteoporotic mouse model. Thus Zfp467 play an important role in ADSCs differentiation to adipocyte and osteoblast. This has relevance to therapeutic interventions in osteoporosis, including si-Zfp467-based therapies currently available, and may be of relevance for the use of adipose-derived stem cells for tissue engineering.

Show MeSH
Related in: MedlinePlus