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6. Epimedium-derived flavonoids promote osteoblastogenesis and suppress adipogenesis in bone marrow stromal cells while exerting an anabolic effect on osteoporotic bone

Author

Songlin, Peng, Peng, Songlin, Ge, Zhang, Zhang, Ge, Yixin, He, He, Yixin, Xinluan, Wang, Wang, Xinluan, Pingchung, Leung, Leung, Pingchung, Kwoksui, Leung, Leung, Kwoksui, Ling, Qin, and Qin, Ling

Subjects
medicine.medical_specialty, Histology, Stromal cell, Physiology, Ovariectomy, Endocrinology, Diabetes and Metabolism, Osteocalcin, Osteoporosis, Bone Marrow Cells, chemistry.chemical_compound, Anabolic Agents, Osteogenesis, Adipocyte, Internal medicine, medicine, Animals, Rats, Wistar, Cells, Cultured, Epimedium, Flavonoids, Adipogenesis, biology, business.industry, Cell Differentiation, medicine.disease, Rats, RUNX2, medicine.anatomical_structure, Endocrinology, chemistry, Ovariectomized rat, biology.protein, Female, Bone marrow, Stromal Cells, business, Biomarkers
Abstract

Background Epimedium-derived flavonoids (EFs) have been reported to prevent bone loss in ovariectomized (OVX) rats and late postmenopausal women but the underlying mechanism of the anabolic effect is unknown. Objective This study aimed to investigate the effect of EFs on osteoporotic bone using histomorphometry and on osteoblastogenesis/adipogenesis of bone marrow stromal cells (BMSCs). Methods 11-month-old female Wistar rats were divided into Sham, OVX, Sham + soluble vehicle (Sham + SV), OVX + SV and OVX + EFs (10 mg/kg/day) groups. 3 months after surgery, rats from the first two groups were euthanized to verify the establishment of OVX-induced osteoporosis. Other groups were orally treated with either daily SV or EFs for 4 months. At sacrifice, serum was analyzed for the levels of osteocalcin and TRACP 5b, BMD in the proximal femur was measured by pQCT. Static and dynamic bone histomorphometry was performed in proximal tibiae with microCT and undecalcified sections, respectively. The effect of EF treatment on differentiation of rat BMSCs was assessed by colony formation assays and gene expression analysis, respectively. Gene expression, ALP activity and adipocyte numbers were determined in differentiating human BMSCs after exposure to conditioned serum from SV- or EFs-treated OVX rats. Results The serum level of osteocalcin was higher and TRACP 5b was lower in EFs versus SV-treated OVX rats. BMD, BV/TV, Tb.N and Conn.D in EFs-treated OVX rats were significantly greater than those of SV-treated OVX rats. Bone histomorphometric parameters OS/BS, MAR, and BFR/BS were significantly higher in EFs versus SV-treated OVX rats. EFs significantly increased osteogenesis and decreased adipogenesis of BMSCs, as evidenced by CFU-ALP and CFU-Adipo assays, respectively. The mRNA level of Runx2 and bone sailoprotein was significantly higher while PPARγ2 was significantly lower in BMSCs from EFs-treated versus SV-treated OVX rats. ALP activity and Runx2 mRNA was significantly higher while adipocyte number and PPARγ2 mRNA was significantly lower in human BMSCs after exposure to conditioned serum from EFs versus SV-treated OVX rats. Conclusion EFs exerted anabolic effect on osteoporotic bone by concomitantly promoting osteogenic and suppressing adipogenic differentiation of BMSCs.

Published
2009

11. Epimedium-derived flavonoids promote osteoblastogenesis and suppress adipogenesis in bone marrow stromal cells while exerting an anabolic effect on osteoporotic bone.

Author

Peng S, Zhang G, He Y, Wang X, Leung P, Leung K, and Qin L

Subjects
Animals, Biomarkers analysis, Bone Marrow Cells cytology, Cell Differentiation, Cells, Cultured, Female, Osteocalcin blood, Osteoporosis metabolism, Ovariectomy, Rats, Rats, Wistar, Stromal Cells cytology, Stromal Cells drug effects, Adipogenesis drug effects, Anabolic Agents pharmacology, Bone Marrow Cells drug effects, Epimedium chemistry, Flavonoids pharmacology, Osteogenesis drug effects, Osteoporosis pathology
Abstract

Background: Epimedium-derived flavonoids (EFs) have been reported to prevent bone loss in ovariectomized (OVX) rats and late postmenopausal women but the underlying mechanism of the anabolic effect is unknown., Objective: This study aimed to investigate the effect of EFs on osteoporotic bone using histomorphometry and on osteoblastogenesis/adipogenesis of bone marrow stromal cells (BMSCs)., Methods: 11-month-old female Wistar rats were divided into Sham, OVX, Sham+soluble vehicle (Sham+SV), OVX+SV and OVX+EFs (10 mg/kg/day) groups. 3 months after surgery, rats from the first two groups were euthanized to verify the establishment of OVX-induced osteoporosis. Other groups were orally treated with either daily SV or EFs for 4 months. At sacrifice, serum was analyzed for the levels of osteocalcin and TRACP 5b, BMD in the proximal femur was measured by pQCT. Static and dynamic bone histomorphometry was performed in proximal tibiae with microCT and undecalcified sections, respectively. The effect of EF treatment on differentiation of rat BMSCs was assessed by colony formation assays and gene expression analysis, respectively. Gene expression, ALP activity and adipocyte numbers were determined in differentiating human BMSCs after exposure to conditioned serum from SV- or EFs-treated OVX rats., Results: The serum level of osteocalcin was higher and TRACP 5b was lower in EFs versus SV-treated OVX rats. BMD, BV/TV, Tb.N and Conn.D in EFs-treated OVX rats were significantly greater than those of SV-treated OVX rats. Bone histomorphometric parameters OS/BS, MAR, and BFR/BS were significantly higher in EFs versus SV-treated OVX rats. EFs significantly increased osteogenesis and decreased adipogenesis of BMSCs, as evidenced by CFU-ALP and CFU-Adipo assays, respectively. The mRNA level of Runx2 and bone sailoprotein was significantly higher while PPARgamma2 was significantly lower in BMSCs from EFs-treated versus SV-treated OVX rats. ALP activity and Runx2 mRNA was significantly higher while adipocyte number and PPARgamma2 mRNA was significantly lower in human BMSCs after exposure to conditioned serum from EFs versus SV-treated OVX rats., Conclusion: EFs exerted anabolic effect on osteoporotic bone by concomitantly promoting osteogenic and suppressing adipogenic differentiation of BMSCs.

Published
2009
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