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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 expressions of specific osteogenic and adipogenic genes. The expressions of specific osteogenic and adipogenic genes in ADSCs were evaluated by real-time RT-PCR at 0, 3, 7 and 14 days after siRNA-Zfp467 transduction. Specific osteogenic marker Osteocalcin (OCN) (A), Osteopontin (OPN) (B), Collagen I (COL I) (C) and bone sialoprotein (BSP) (D) were up-regulated in si-Zfp467 transduced cells. Specific adipogenic marker lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor gamma (PPARγ) were down-regulated in si-Zfp467 transduced cells (Mean ± SEM, n = 3). * p < 0.05 vs. control group; ** p < 0.01 vs. control group.
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Figure 5: The expressions of specific osteogenic and adipogenic genes. The expressions of specific osteogenic and adipogenic genes in ADSCs were evaluated by real-time RT-PCR at 0, 3, 7 and 14 days after siRNA-Zfp467 transduction. Specific osteogenic marker Osteocalcin (OCN) (A), Osteopontin (OPN) (B), Collagen I (COL I) (C) and bone sialoprotein (BSP) (D) were up-regulated in si-Zfp467 transduced cells. Specific adipogenic marker lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor gamma (PPARγ) were down-regulated in si-Zfp467 transduced cells (Mean ± SEM, n = 3). * p < 0.05 vs. control group; ** p < 0.01 vs. control group.

Mentions: As mentioned above, in two representative subclones, Zfp467 shRNA-2 caused more profound reduction of Zfp467 gene expression when compared to shRNA-1. Hereafter, we mainly used the Zfp467 shRNA-2 subline for further analysis. The expressions of specific osteogenic and adipogenic genes were evaluated by real-time RT-PCR at 0, 3, 7 and 14 days post-transduction. Our results indicated that specific osteogenic marker Osteocalcin (OCN), Osteopontin (OPN), Collagen I (COL I) and bone sialoprotein (BSP) were up-regulated in si-Zfp467 transduced cells (Figure 5A-D). Specific adipogenic marker lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor gamma (PPARγ) were down-regulated in si-Zfp467 transduced cells (Figure 5E-F). The statistical analysis showed that the plasmid Zfp467 shRNA could have significant inhibitive effects on the mRNA levels of specific adipogenic gene at day 7 and 14 when compared with that of adipogenic gene at day 0 and 3 (p < 0.05 and p < 0.01, respectively) (Figure 5A-D), however, RNA interfere of Zfp467 significantly enhanced the mRNA levels of specific osteogenic gene at day 7 and 14 when compared with that of osteogenic gene at day 0 and 3 (p < 0.05 and p < 0.01, respectively) (Figure 5E-F), which suggested Zfp467 involved in the ADSCs differentiated into adipocytes and osteoblasts.


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 expressions of specific osteogenic and adipogenic genes. The expressions of specific osteogenic and adipogenic genes in ADSCs were evaluated by real-time RT-PCR at 0, 3, 7 and 14 days after siRNA-Zfp467 transduction. Specific osteogenic marker Osteocalcin (OCN) (A), Osteopontin (OPN) (B), Collagen I (COL I) (C) and bone sialoprotein (BSP) (D) were up-regulated in si-Zfp467 transduced cells. Specific adipogenic marker lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor gamma (PPARγ) were down-regulated in si-Zfp467 transduced cells (Mean ± SEM, n = 3). * p < 0.05 vs. control group; ** p < 0.01 vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: The expressions of specific osteogenic and adipogenic genes. The expressions of specific osteogenic and adipogenic genes in ADSCs were evaluated by real-time RT-PCR at 0, 3, 7 and 14 days after siRNA-Zfp467 transduction. Specific osteogenic marker Osteocalcin (OCN) (A), Osteopontin (OPN) (B), Collagen I (COL I) (C) and bone sialoprotein (BSP) (D) were up-regulated in si-Zfp467 transduced cells. Specific adipogenic marker lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor gamma (PPARγ) were down-regulated in si-Zfp467 transduced cells (Mean ± SEM, n = 3). * p < 0.05 vs. control group; ** p < 0.01 vs. control group.
Mentions: As mentioned above, in two representative subclones, Zfp467 shRNA-2 caused more profound reduction of Zfp467 gene expression when compared to shRNA-1. Hereafter, we mainly used the Zfp467 shRNA-2 subline for further analysis. The expressions of specific osteogenic and adipogenic genes were evaluated by real-time RT-PCR at 0, 3, 7 and 14 days post-transduction. Our results indicated that specific osteogenic marker Osteocalcin (OCN), Osteopontin (OPN), Collagen I (COL I) and bone sialoprotein (BSP) were up-regulated in si-Zfp467 transduced cells (Figure 5A-D). Specific adipogenic marker lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor gamma (PPARγ) were down-regulated in si-Zfp467 transduced cells (Figure 5E-F). The statistical analysis showed that the plasmid Zfp467 shRNA could have significant inhibitive effects on the mRNA levels of specific adipogenic gene at day 7 and 14 when compared with that of adipogenic gene at day 0 and 3 (p < 0.05 and p < 0.01, respectively) (Figure 5A-D), however, RNA interfere of Zfp467 significantly enhanced the mRNA levels of specific osteogenic gene at day 7 and 14 when compared with that of osteogenic gene at day 0 and 3 (p < 0.05 and p < 0.01, respectively) (Figure 5E-F), which suggested Zfp467 involved in the ADSCs differentiated into adipocytes and osteoblasts.

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