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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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Effects of systemic transplantation of ADSCs on OVX-induced osteoclasts formation and bone destruction. Tibiae from sham-operated (sham) and OVX (OVX, OVX + Scrambled siRNA and OVX + si-Zfp467) mice were examined by μCT. 3D reconstruction of tibiae revealed that bone mass in OVX mice treated with si-Zfp467 ADSCs (OVX + si-Zfp467) significantly increased when compared with that in OVX or ADSCs (with scrambled siRNA) transplanted OVX mice. (A-C) Histograms represent the 3D trabecular structural parameters in tibiae: bone volume fraction (BV/TV), trabecular number (Tb.N), and bone mineral densities (BMD). (D) The levels of DPD in four groups were assayed by competitive enzyme immunoassay using the MicroVue DPD EIA kit. (E) OC number (no.) per bone surface (NOc/BS) was using to indicate quantification of OC cells. (F) OB number per bone surface (NOb/BS) was using to indicate quantification of OB cells. *P < 0.01, **P < 0.05. Data represent mean ± SD. n = 6.
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Figure 6: Effects of systemic transplantation of ADSCs on OVX-induced osteoclasts formation and bone destruction. Tibiae from sham-operated (sham) and OVX (OVX, OVX + Scrambled siRNA and OVX + si-Zfp467) mice were examined by μCT. 3D reconstruction of tibiae revealed that bone mass in OVX mice treated with si-Zfp467 ADSCs (OVX + si-Zfp467) significantly increased when compared with that in OVX or ADSCs (with scrambled siRNA) transplanted OVX mice. (A-C) Histograms represent the 3D trabecular structural parameters in tibiae: bone volume fraction (BV/TV), trabecular number (Tb.N), and bone mineral densities (BMD). (D) The levels of DPD in four groups were assayed by competitive enzyme immunoassay using the MicroVue DPD EIA kit. (E) OC number (no.) per bone surface (NOc/BS) was using to indicate quantification of OC cells. (F) OB number per bone surface (NOb/BS) was using to indicate quantification of OB cells. *P < 0.01, **P < 0.05. Data represent mean ± SD. n = 6.

Mentions: We performed μCT analysis to determine the impact of ADSCs and Zfp467 on OVX-induced osteoporotic mice. Systemic transplantation of ADSCs with si-Zfp467 into OVX mice prevented OVX-induced bone loss in mice. When compared with OVX or ADSCs (with scrambled siRNA)-transplanted OVX mice, bone loss indices, including bone volume fraction, trabecular number, and bone mineral density in si-Zfp467-ADSCs transplanted OVX mice were restored to normal (the level of sham-operated mice) (Figure 6A-C).


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)

Effects of systemic transplantation of ADSCs on OVX-induced osteoclasts formation and bone destruction. Tibiae from sham-operated (sham) and OVX (OVX, OVX + Scrambled siRNA and OVX + si-Zfp467) mice were examined by μCT. 3D reconstruction of tibiae revealed that bone mass in OVX mice treated with si-Zfp467 ADSCs (OVX + si-Zfp467) significantly increased when compared with that in OVX or ADSCs (with scrambled siRNA) transplanted OVX mice. (A-C) Histograms represent the 3D trabecular structural parameters in tibiae: bone volume fraction (BV/TV), trabecular number (Tb.N), and bone mineral densities (BMD). (D) The levels of DPD in four groups were assayed by competitive enzyme immunoassay using the MicroVue DPD EIA kit. (E) OC number (no.) per bone surface (NOc/BS) was using to indicate quantification of OC cells. (F) OB number per bone surface (NOb/BS) was using to indicate quantification of OB cells. *P < 0.01, **P < 0.05. Data represent mean ± SD. n = 6.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Effects of systemic transplantation of ADSCs on OVX-induced osteoclasts formation and bone destruction. Tibiae from sham-operated (sham) and OVX (OVX, OVX + Scrambled siRNA and OVX + si-Zfp467) mice were examined by μCT. 3D reconstruction of tibiae revealed that bone mass in OVX mice treated with si-Zfp467 ADSCs (OVX + si-Zfp467) significantly increased when compared with that in OVX or ADSCs (with scrambled siRNA) transplanted OVX mice. (A-C) Histograms represent the 3D trabecular structural parameters in tibiae: bone volume fraction (BV/TV), trabecular number (Tb.N), and bone mineral densities (BMD). (D) The levels of DPD in four groups were assayed by competitive enzyme immunoassay using the MicroVue DPD EIA kit. (E) OC number (no.) per bone surface (NOc/BS) was using to indicate quantification of OC cells. (F) OB number per bone surface (NOb/BS) was using to indicate quantification of OB cells. *P < 0.01, **P < 0.05. Data represent mean ± SD. n = 6.
Mentions: We performed μCT analysis to determine the impact of ADSCs and Zfp467 on OVX-induced osteoporotic mice. Systemic transplantation of ADSCs with si-Zfp467 into OVX mice prevented OVX-induced bone loss in mice. When compared with OVX or ADSCs (with scrambled siRNA)-transplanted OVX mice, bone loss indices, including bone volume fraction, trabecular number, and bone mineral density in si-Zfp467-ADSCs transplanted OVX mice were restored to normal (the level of sham-operated mice) (Figure 6A-C).

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