Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites

Autor: S. F. Zhang, T. L. Nelson, Su-Li Cheng, Pamela M. Warlow, Roberto Civitelli
Rok vydání: 1994
Předmět:
musculoskeletal diseases
Bone sialoprotein
medicine.medical_specialty
Sialoglycoproteins
Endocrinology
Diabetes and Metabolism
Metabolite
Bone Marrow Cells
Dexamethasone
Bone resorption
Bone remodeling
Structure-Activity Relationship
chemistry.chemical_compound
Calcification
Physiologic
Endocrinology
Bone Marrow
Internal medicine
medicine
Humans
Integrin-Binding Sialoprotein
Orthopedics and Sports Medicine
RNA
Messenger
Osteopontin
Cells
Cultured
Analysis of Variance
Extracellular Matrix Proteins
Osteoblasts
biology
Stem Cells
Gene Expression Regulation
Developmental
Nucleic Acid Hybridization
Cell Differentiation
Osteoblast
Alkaline Phosphatase
Blotting
Northern
Isoflavones
medicine.anatomical_structure
chemistry
biology.protein
Osteocalcin
Cytokines
Calcium
Proteoglycans
Collagen
Decorin
Stromal Cells
Ipriflavone
medicine.drug
Zdroj: Calcified Tissue International. 55:356-362
ISSN: 1432-0827
0171-967X
DOI: 10.1007/bf00299315
Popis: Ipriflavone (IP), an isoflavone derivative, has been shown to interfere with bone remodeling by inhibiting bone resorption and perhaps stimulating bone formation. In this study, we have analyzed the effect of IP and its metabolites on the differentiation and function of human osteoblastic cells. Bone marrow stromal osteoprogenitor cells (BMC) and trabecular bone osteoblasts (HOB) were isolated from human donors. The former can be induced to differentiate by treatment with dexamethasone, whereas the latter represent a more differentiated osteoblast. Incubation of BMC with metabolite III (10(-5) M) for 1 week induced modest but significant changes of alkaline phosphatase activity. Though both IP and metabolite III stimulated the expression of bone sialoprotein mRNA, a protein involved in cell attachment to the matrix, only metabolite III increased the steady-state level of decorin mRNA, a collagen fibrillogenesis-regulating proteoglycan. Metabolites III and V, but not the other isoflavones, increased the expression of type I collagen mRNA in HOB, whereas no detectable changes were observed in BMC cells with any of the experimental compounds. In HOB, an increased abundance of osteopontin and bone sialoprotein mRNA were also obtained after 1-week treatment with IP or metabolite V. No appreciable effects of IP or its metabolites were seen on osteocalcin expression and synthesis by either cell type. Finally, IP consistently increased the amount of 45Ca incorporated into the cell layer by BMC, and stimulated mineralization of both BMC and HOB, assessed by von Kossa staining. Thus, IP and its metabolites regulate the differentiation and biosynthetic properties of human bone-forming cells by enhancing the expression of some important matrix proteins and facilitating the mineralization process.
Databáze: OpenAIRE
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