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The osteoprotective effect of psoralen in ovariectomy-induced osteoporotic rats via stimulating the osteoblastic differentiation from bone mesenchymal stem cells

Yang, Zhu MD1; Huang, Jian-hua PhD2; Liu, Shu-fen MD1; Zhao, Yong-jian BS1; Shen, Zi-yin BS2; Wang, Yong-jun PhD1; Bian, Qin PhD1,2

doi: 10.1097/gme.0b013e3182507e18
Original Articles

Objective: Psoralea corylifolia extract has been reported to promote bone formation in osteoporotic animals. Psoralen (PSO), a flavonoid glycoside, as the active component of P corylifolia L, is effective in increasing new bone-forming osteoblasts in parietal bone defects. However, the effect and molecular mechanisms of PSO on bone mesenchymal stem cells (bMSCs) in the osteoporotic state are widely unknown. This study was designed to evaluate the osteoprotective effect of PSO in ovariectomy (OVX)-induced rats and to seek possible molecular mechanisms of PSO in bMSCs.

Methods: We observed the osteogenic effect of PSO (3-month treatment) on osteoporotic rat models induced by OVX via testing bone densitometry, histomorphometries, and immunohistochemistry in vivo. Alkaline phosphatase staining and colony-forming unit-fibroblast and colony-forming unit-adipocyte assays were performed to evaluate the differentiation potential of bMSCs ex vivo. In addition, the molecular targets of PSO in bMSCs were detected by stem cell microarray analysis of 256 genes and confirmed by real-time reverse transcription–polymerase chain reaction.

Results: Micro-CT morphometry analysis showed that PSO significantly improved bone mass indicators including increased trabecular thickness and decreased trabecular space. Meanwhile, PSO elevated the well-known osteogenic marker osteocalcin level in OVX-induced osteoporotic rats. Next, in ex vivo studies, we revealed that PSO facilitated alkaline phosphatase staining and increased the colony-forming unit-fibroblasts. Based on gene expression profile analysis, we screened a set of genes dysregulated in OVX but reversed by PSO treatment. These genes were highly enriched in the Notch signaling pathway, which was documented to play a role in bMSC differentiation.

Conclusions: Our findings show that PSO promotes bone mass in OVX-induced osteoporotic rats. This effect of PSO is highly related to the stimulation of differentiation of bMSCs to osteoblasts.

From the 1Department of Orthopaedics and Traumatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and 2Institute of Integrated Traditional Chinese Medicine and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Received November 24, 2011; revised and accepted February 15, 2012.

Z.Y. and J.-H.H. contributed equally to this work.

Q.B. and Y.-J.H. are both corresponding authors.

Funding/support: This work was supported by the National Basic Research Program in China (973 Plan, 2010CB530402, 2010CB530404), the International Cooperation Programs of National Natural Science Foundation of China (30710103904), a National Natural Foundation Committee of China key grant (30930111), the Project of National Natural Science Foundation of China (81001526), Shanghai Science and Technology Development Funds (11QA1406600), Theories and Therapies Bones Province Key Laboratory of Ministry of Education, Shanghai University, Shanghai Education Commission Innovation Team Program Section 6 (2009), and Ministry of Education senior personnel items: Professor Changjiang Scholar Program (teaching people, 2009, 17).

Financial disclosure/conflicts of interest: None reported.

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Address correspondence to: Qin Bian, PhD, or Yong-jun Wang, PhD, Department of Orthopaedics and Traumatology, Longhua Hospital, and Institute of Spine, Shanghai University of Traditional Chinese Medicine, No. 725 South Wan-ping Road, Shanghai 200032, China. E-mail: bianqin213@126.com

©2012The North American Menopause Society