The osteoprotective effect of psoralen in ovariectomy-induced osteoporotic rats via stimulating the osteoblastic differentiation from bone mesenchymal stem cells.
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.
Department of Orthopaedics and Traumatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Zhu
Z
Yang
Jian-hua
JH
Huang
Shu-fen
SF
Liu
Yong-jian
YJ
Zhao
Zi-yin
ZY
Shen
Yong-jun
YJ
Wang
Qin
Q
Bian
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002454:Cell Differentiation / Q000502:physiology; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005363:Ficusin / Q000494:pharmacology*; D015870:Gene Expression; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D046228:Microarray Analysis; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed
D017931:DNA Primers; D017319:Photosensitizing Agents; D015675:Osteocalcin; D005363:Ficusin