title: Resveratrol Increases Osteoblast Differentiation In Vitro Independently of Inflammation.
abstract: Low-grade inflammation negatively affects bone. Resveratrol is a natural compound proven to possess both anti-inflammatory and bone protective properties. However, it is uncertain if the bone effects are mediated though anti-inflammatory effects. Firstly, we investigated if resveratrol affects proliferation and differentiation of human bone marrow-derived mesenchymal stem cells. Secondly, we investigated if inflammation negatively affects proliferation and differentiation, and if resveratrol counteracts this through anti-inflammatory effects. Mesenchymal stem cells were obtained from bone marrow aspiration in 13 healthy individuals and cultured towards the osteoblast cell lineage. The cells were stimulated with resveratrol, lipopolysaccharide (LPS), LPS + resveratrol, or vehicle (control) for 21 days. Compared to control, resveratrol decreased cell number by 35 % (p < 0.05) and induced differentiation (a 3-fold increase in alkaline phosphatase (p < 0.002), while P1NP and OPG showed similar trends). LPS induced inflammation with a 44-fold increase in interleukin-6 (p < 0.05) and an extremely prominent increase in interleukin-8 production (p < 0.05) relative to control. In addition, LPS increased cell count (p < 0.05) and decreased differentiation (a reduction in P1NP production (p < 0.02)). Co-stimulation with LPS + resveratrol did not reduce interleukin-6 or interleukin-8, but nonetheless, cell count was reduced (p < 0.05) and alkaline phosphatase, P1NP, and OPG increased (p < 0.05 for all). Thus, resveratrol stimulates osteoblast differentiation independently of inflammation.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage-Hansens Gade 2, Entrance 3C, 8000, Aarhus, Denmark. marie.juul.ornstrup@clin.au.dk.|Department of Clinical Medicine, Aarhus University, Nordre Ringgade 1, 8000, Aarhus, Denmark. marie.juul.ornstrup@clin.au.dk.
authors.forename: Marie Juul
authors.initials: MJ
authors.lastname: Ornstrup
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage-Hansens Gade 2, Entrance 3C, 8000, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Nordre Ringgade 1, 8000, Aarhus, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Harsløf
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage-Hansens Gade 2, Entrance 3C, 8000, Aarhus, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Sørensen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage-Hansens Gade 2, Entrance 3C, 8000, Aarhus, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Stenkjær
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage-Hansens Gade 2, Entrance 3C, 8000, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Nordre Ringgade 1, 8000, Aarhus, Denmark.
authors.forename: Bente Lomholt
authors.initials: BL
authors.lastname: Langdahl
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage-Hansens Gade 2, Entrance 3C, 8000, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Nordre Ringgade 1, 8000, Aarhus, Denmark.
authors.forename: Steen Bønløkke
authors.initials: SB
authors.lastname: Pedersen
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D013267:Stilbenes; D015675:Osteocalcin; D000077185:Resveratrol
keywords: Alkaline phosphatase; Differentiation; Inflammation; Osteoblast; Proliferation; Resveratrol