PMID- 14961210 OWN - NLM STAT- MEDLINE DCOM- 20041223 LR - 20220409 IS - 0171-967X (Print) IS - 0171-967X (Linking) VI - 74 IP - 5 DP - 2004 May TI - Mechanical stimulation promotes osteogenic differentiation of human bone marrow stromal cells on 3-D partially demineralized bone scaffolds in vitro. PG - 458-68 AB - Bone is a dynamic tissue that is able to sense and adapt to mechanical stimuli by modulating its mass, geometry, and structure. Bone marrow stromal cells (BMSCs) are known to play an integral part in bone formation by providing an osteoprogenitor cell source capable of differentiating into mature osteoblasts in response to mechanical stresses. Characteristics of the in vivo bone environment including the three dimensional (3-D) lacunocanalicular structure and extracellular matrix composition have previously been shown to play major roles in influencing mechanotransduction processes within bone cells. To more accurately model this phenomenon in vitro, we cultured human BMSCs on 3-D, partially demineralized bone scaffolds in the presence of four-point bending loads within a novel bioreactor. The effect of mechanical loading and dexamethasone concentration on BMSC osteogenic differentiation and mineralized matrix production was studied for 8 and 16 days of culture. Mechanical stimulation after 16 days with 10 nM dexamethasone promoted osteogenic differentiation of BMSCs by significantly elevating alkaline phosphatase activity as well as alkaline phosphatase and osteopontin transcript levels over static controls. Mineralized matrix production also increased under these culture conditions. Dexamethasone concentration had a dramatic effect on the ability of mechanical stimulation to modulate these phenotypic and genotypic responses. These results provide increased insight into the role of mechanical stimulation on osteogenic differentiation of human BMSCs in vitro and may lead to improved strategies in bone tissue engineering. FAU - Mauney, J R AU - Mauney JR AD - Tufts University, Department of Biomedical Engineering, Biotechnology Center, 4 Colby Street, Medford, Massachusetts 02155, USA. FAU - Sjostorm, S AU - Sjostorm S FAU - Blumberg, J AU - Blumberg J FAU - Horan, R AU - Horan R FAU - O'Leary, J P AU - O'Leary JP FAU - Vunjak-Novakovic, G AU - Vunjak-Novakovic G FAU - Volloch, V AU - Volloch V FAU - Kaplan, D L AU - Kaplan DL LA - eng PT - Comparative Study PT - Journal Article DEP - 20040217 PL - United States TA - Calcif Tissue Int JT - Calcified tissue international JID - 7905481 RN - 0 (Glucocorticoids) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Adult MH - Alkaline Phosphatase/metabolism MH - Bone Demineralization Technique MH - Bone Marrow Cells/*cytology/drug effects MH - Bone Matrix/drug effects/physiology MH - Cell Differentiation/drug effects/*physiology MH - Cells, Cultured MH - Compressive Strength/drug effects MH - Dexamethasone/pharmacology MH - Dose-Response Relationship, Drug MH - Glucocorticoids/pharmacology MH - Humans MH - Osteogenesis/drug effects/*physiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stress, Mechanical MH - Stromal Cells/*cytology/drug effects MH - Tensile Strength/drug effects MH - Tissue Engineering/instrumentation/*methods EDAT- 2004/02/13 05:00 MHDA- 2004/12/24 09:00 CRDT- 2004/02/13 05:00 PHST- 2003/09/21 00:00 [received] PHST- 2003/10/03 00:00 [accepted] PHST- 2004/02/13 05:00 [pubmed] PHST- 2004/12/24 09:00 [medline] PHST- 2004/02/13 05:00 [entrez] AID - 10.1007/s00223-003-0104-7 [doi] PST - ppublish SO - Calcif Tissue Int. 2004 May;74(5):458-68. doi: 10.1007/s00223-003-0104-7. Epub 2004 Feb 17.