Abstract
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.
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References
A Heinonen H Sievanen H Kyrolainen J Perttunen P Kannus (2001) ArticleTitleMineral mass, size, and estimated mechanical strength of triple jumpers’ lower limb. Bone 29 279–285 Occurrence Handle10.1016/S8756-3282(01)00574-9 Occurrence Handle1:STN:280:DC%2BD3MrgvFynsw%3D%3D Occurrence Handle11557373
E Tanck J Homminga GH Lenthe Particlevan R Huiskes (2001) ArticleTitleIncrease in bone volume fraction precedes architectural adaptation in growing bone. Bone 28 650–654 Occurrence Handle10.1016/S8756-3282(01)00464-1 Occurrence Handle1:STN:280:DC%2BD3MzmsFSgtQ%3D%3D Occurrence Handle11425654
DB Burr C Milgrom D Fyhrie M Forwood M Nyska et al. (1996) ArticleTitle In vivo measurement of human tibial strains during vigorous activity. Bone 18 405–410 Occurrence Handle10.1016/8756-3282(96)00028-2 Occurrence Handle1:STN:280:BymA3Mbhsl0%3D Occurrence Handle8739897
L Wang SP Fritton SC Cowin S Weinbaum (1999) ArticleTitleFluid pressure relaxation depends upon osteonal microstructure: modeling an oscillatory bending experiment. J Biomech 32 663–672 Occurrence Handle10.1016/S0021-9290(99)00059-7 Occurrence Handle1:STN:280:DyaK1MzisF2nsg%3D%3D Occurrence Handle10400353
ML Knothe Tate R Steck MR Forwood P Niederer (2000) ArticleTitle In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation. J Exp Biol 203 2737–2745
LA MacGinitie GD Stanely WA Bieber DD Wu (1997) ArticleTitleBone streaming potentials and currents depend on anatomical structure and loading orientation. J Biomech 30 1133–1139 Occurrence Handle10.1016/S0021-9290(97)85605-9 Occurrence Handle1:STN:280:DyaK1c7hslCqtQ%3D%3D Occurrence Handle9456381
BR Beck YX Qin KJ McLeod MW Otter (2002) ArticleTitleOn the relationship between streaming potential and strain in an in vivo bone preparation. Calcif Tissue Int 71 335–343
J Klein-Nulend CM Semeins EH Burger (1996) ArticleTitleProstaglandin mediated modulation of transforming growth factor-metabolism in primary mouse osteoblastic cells in vitro. J Cell Physiol 168 1–7 Occurrence Handle10.1002/(SICI)1097-4652(199607)168:1<1::AID-JCP1>3.0.CO;2-T Occurrence Handle1:CAS:528:DyaK28XjvVSqu7o%3D Occurrence Handle8647903
Q Wang S Zhong J Ouyang L Jiang Z Zhang et al. (1998) ArticleTitleOsteogenesis of electrically stimulated bone cells mediated in part by calcium ions. Clin Orthop 348 259–268 Occurrence Handle9553560
R Smalt FT Mitchell RL Howard TJ Chambers (1997) ArticleTitleInduction of NO and prostaglandin E2 in osteoblasts by wall-shear stress but not mechanical strain. Am J Physiol 273 751–758
M Hartig U Joos HP Wiesmann (2000) ArticleTitleCapacitively coupled electric fields accelerate proliferation of osteoblast-like primary cells and increase bone extracellular matrix formation in vitro. Eur Biophys J 29 499–506 Occurrence Handle10.1007/s002490000100 Occurrence Handle1:CAS:528:DC%2BD3cXosVOls7s%3D Occurrence Handle11156291
CD Toma S Ashkar ML Gray JL Schaffer LC Gerstenfeld (1997) ArticleTitleSignal transduction of mechanical stimuli is dependent on microfilament integrity: identification of osteopontin as a mechanically induced gene in osteoblasts. J Bone Miner Res 12 1626–1636 Occurrence Handle1:CAS:528:DyaK2sXmvVSkt7k%3D Occurrence Handle9333123
D Murray N Rushton (1990) ArticleTitleThe effect of strain on bone cell prostaglandin E2 release: a new experimental method. Calcif Tissue Int 47 35–39
C Neidlinger-Wilke H Wilke L Claes (1994) ArticleTitleCyclic stretching of human osteoblasts affects proliferation and metabolism: a new experimental method and its applications. J Orthop Res 12 70–78 Occurrence Handle1:STN:280:ByuC2Mjnt1Y%3D Occurrence Handle8113944
C Brighton B Strafford S Gross D Leatherwood J Williams et al. (1991) ArticleTitleThe proliferative and synthetic response of isolated calvarial bone cells of rats to cyclic biaxial mechanical strain. J Bone Joint Surg 73 320–331 Occurrence Handle1:STN:280:By6C287mtlw%3D Occurrence Handle1848246
H Glantschnig F Varga M Rumpler K Klaushofer (1996) ArticleTitleProstacyclin (PGI2): a potential mediator of c-fos expression induced by hydrostatic pressure in osteoblastic cells. Eur J Clin Invest 26 544–548 Occurrence Handle10.1046/j.1365-2362.1996.165312.x Occurrence Handle1:CAS:528:DyaK28Xltlaiu7Y%3D Occurrence Handle8864415
J Klein-Nulend J Roelofsen C Semeins A Bronckers E Burger (1997) ArticleTitleMechanical stimulation of osteopontin mRNA expression and synthesis in bone cell cultures. J Cell Physiol 170 174–181 Occurrence Handle10.1002/(SICI)1097-4652(199702)170:2<174::AID-JCP9>3.0.CO;2-L Occurrence Handle1:CAS:528:DyaK2sXhtVeltro%3D Occurrence Handle9009146
I Owan D Burr C Turner J Qiu Y Tu et al. (1997) ArticleTitleMechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain. Am J Physiol 273 810–815
K Sakai M Mohtai Y Iwamoto (1998) ArticleTitleFluid shear stress increases transforming growth factor beta 1 expression in human osteoblast-like cells: modulation by cation channel blockades. Calcif Tissue Int 63 515–520 Occurrence Handle10.1007/s002239900567 Occurrence Handle9817947
I Westbroek NE Ajubi MJ Albas CM Semeins J Klein-Nulend et al. (2000) ArticleTitleDifferential stimulation of prostaglandin G/H synthase-2 in osteocytes and other osteogenic cells by pulsating fluid flow. Biochem Biophys Res Commun 268 414–419 Occurrence Handle10.1006/bbrc.2000.2154 Occurrence Handle1:CAS:528:DC%2BD3cXhtFGjt7s%3D Occurrence Handle10679219
EH Burger J Klein-Nulend (1999) ArticleTitleMechanotransduction in bone—role of the lacuno-canalicular network. FASEB J 13 S101–112 Occurrence Handle1:CAS:528:DyaK1MXjtFGku7c%3D
VI Sikavitsas JS Temenoff AG Mikos (2001) ArticleTitleBiomaterials and bone mechanotransduction. Biomaterials 22 2581–2593 Occurrence Handle10.1016/S0142-9612(01)00002-3 Occurrence Handle1:CAS:528:DC%2BD3MXlsFymu7s%3D Occurrence Handle11519777
RS Carvalho JL Schaffer LC Gerstenfeld (1998) ArticleTitleOsteoblasts induce osteopontin expression in response to attachment on fibronectin: demonstration of a common role for integrin receptors in the signal transduction processes of cell attachment and mechanical stimulation. J Cell Biochem 70 376–390 Occurrence Handle10.1002/(SICI)1097-4644(19980901)70:3<376::AID-JCB11>3.0.CO;2-J Occurrence Handle1:CAS:528:DyaK1cXkvFCqsLY%3D Occurrence Handle9706875
T Davisson S Kunig A Chen R Sah A Ratcliffe (2002) ArticleTitleStatic and dynamic compression modulate matrix metabolism in tissue engineered cartilage. J Orthop Res 20 842–848 Occurrence Handle10.1016/S0736-0266(01)00160-7 Occurrence Handle1:CAS:528:DC%2BD38XltlertLg%3D Occurrence Handle12168676
GH Altman RL Horan I Martin J Farhadi PR Stark et al. (2002) ArticleTitleCell differentiation by mechanical stress. FASEB J 16 270–272 Occurrence Handle1:CAS:528:DC%2BD38XhsVCjsb8%3D Occurrence Handle11772952
BS Kim DJ Mooney (2000) ArticleTitleScaffolds for engineering smooth muscle under cyclic mechanical strain conditions. J Biomech Eng 122 210–215 Occurrence Handle10.1115/1.429651 Occurrence Handle1:STN:280:DC%2BD3M%2Fkt1Wmsw%3D%3D Occurrence Handle10923287
WH Zimmermann K Schneiderbanger P Schubert M Didie F Munzel et al. (2002) ArticleTitleTissue engineering of a differentiated cardiac muscle construct. Circ Res 90 223–230 Occurrence Handle10.1161/hh0202.103644 Occurrence Handle1:CAS:528:DC%2BD38Xhtl2lsro%3D Occurrence Handle11834716
K Tang G Dang Z Guo (2002) ArticleTitleThe effects of intermittent hydromechanics on the differentiation and function of bone marrow stromal derived osteoblasts in porous calcium phosphate ceramics. Zhonghua Yi Xue Za Zhi 82 665–668 Occurrence Handle1:CAS:528:DC%2BD38XptFSgsL8%3D Occurrence Handle12133462
Y Yang JL Magnay L Cooling HA El (2002) ArticleTitleDevelopment of a “mechano-active” scaffold for tissue engineering. Biomaterials 23 2119–2126 Occurrence Handle10.1016/S0142-9612(01)00342-8 Occurrence Handle1:CAS:528:DC%2BD38XhvVWhs7Y%3D Occurrence Handle11962652
SE Haynesworth J Goshima VM Goldberg AI Caplan (1992) ArticleTitleCharacterization of cells with osteogenic potential from human marrow. Bone 13 81–88 Occurrence Handle1:STN:280:By2B2Mngs1Y%3D Occurrence Handle1581112
DJ Prockop (1997) ArticleTitleMarrow stromal cells as stem cells for nonhematopietic tissues. Science 276 71–74 Occurrence Handle1:CAS:528:DyaK2sXitlyqt7g%3D Occurrence Handle9082988
AI Caplan DJ Fink T Goto AE Linton RG Young et al. (.) Mesenchymal stem cells and tissue repair. The anterior cruciate ligament: current and future concepts Raven Press N.Y.
JN Beresford JH Bennett C Devlin PS Leboy ME Owen (1992) ArticleTitleEvidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow. J Cell Sci 102 341–351 Occurrence Handle1:CAS:528:DyaK38XlsVekt7w%3D Occurrence Handle1400636
S Wakitani T Goto SJ Pineda RG Young JM Mansour et al. (1994) ArticleTitleMesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg 76 579–592 Occurrence Handle1:STN:280:ByuB3c7itF0%3D Occurrence Handle8150826
B Seshi S Kumar D Sellers (2000) ArticleTitleHuman bone marrow stromal cell: coexpression of markers specific for multiple mesenchymal cell lineages. Blood Cells Mol Dis 26 234–246 Occurrence Handle10.1006/bcmd.2000.0301 Occurrence Handle1:CAS:528:DC%2BD3cXlslCqtbk%3D Occurrence Handle10950944
P Bianco P Gehron Robey (2000) ArticleTitleMarrow stromal stem cells. J Clin Invest 105 1663–1668 Occurrence Handle1:CAS:528:DC%2BD3cXkt1Wqs74%3D Occurrence Handle10862779
GP Thomas AJ el Haj (1996) ArticleTitleBone marrow stromal cells are load responsive in vitro. Calcif Tissue Int 58 101–108
T Yoshikawa SA Peel JR Gladstone JE Davies (1997) ArticleTitleBiochemical analysis of the response in rat bone marrow cell cultures to mechanical stimulation. Biomed Mater Eng 7 369–377
GN Bancroft VI Sikavitsas J Dolder Particlevan den TL Sheffield CG Ambrose et al. (2002) ArticleTitleFluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc Natl Acad Sci U S A 99 12600–12605 Occurrence Handle10.1073/pnas.202296599 Occurrence Handle1:CAS:528:DC%2BD38XnvFGiu7g%3D Occurrence Handle12242339
M Wozniak A Fausto CP Carron DM Meyer KA Hruska (2000) ArticleTitleMechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3-integrin expression. J Bone Miner Res 15 1731–1745 Occurrence Handle1:CAS:528:DC%2BD3cXmsF2mtL4%3D Occurrence Handle10976993
JR Mauney J Blumberg M Pirun V Volloch G Vunjak-Novakovic et al. (2003) ArticleTitleOsteogenic differentiation of human bone marrow stromal cells on partially demineralized bone scaffolds in vitro. Tissue Eng 00 00
CH Turner MP Akhter DM Raab DB Kimmel RR Recker (1991) ArticleTitleA noninvasive, in vivo model for studying strain adaptive bone modeling. Bone 12 73–79 Occurrence Handle1:STN:280:By6B1M7ltF0%3D Occurrence Handle2064843
MP Akhter DM Raab CH Turner DB Kimmel RR Recker (1992) ArticleTitleCharacterization of in vivo strain in the rat tibia during external application of a four-point bending load. J Biomech 25 1241–1246 Occurrence Handle1:STN:280:ByyD3MnhvVU%3D Occurrence Handle1400526
DM Cullen RT Smith MP Akhter (2001) ArticleTitleBone-loading response varies with strain magnitude and cycle number. J Appl Physiol 91 1971–1976
RR Miles CH Turner R Santerre Y Tu P McClelland et al. (1998) ArticleTitleAnalysis of differential gene expression in rat tibia after an osteogenic stimulus in vivo: mechanical loading regulates osteopontin and myeloperoxidase. J Cell Biochem 68 355–365 Occurrence Handle10.1002/(SICI)1097-4644(19980301)68:3<355::AID-JCB6>3.0.CO;2-T Occurrence Handle1:CAS:528:DyaK1cXosVWitA%3D%3D Occurrence Handle9518261
R Rosenthal J Folkman J Glowacki (1999) ArticleTitleDemineralized bone implants for nonunion fractures, bone cysts, and fibrous lesions. Clin Orthop 364 61–69 Occurrence Handle10.1097/00003086-199907000-00009 Occurrence Handle10416393
G Vunjak-Novakovic B Obradovic I Martin PM Bursac R Langer et al. (1998) ArticleTitleDynamic cell seeding of polymer scaffolds for cartilage tissue engineering. Biotechnol Prog 14 193–202 Occurrence Handle10.1021/bp970120j Occurrence Handle1:CAS:528:DyaK1cXhs1Grsrg%3D Occurrence Handle9548769
Gere JM (1990) Mechanics of materials. PWS-KENT Pub. Co, Boston.
N Jaiswal SE Haynesworth AI Caplan SP Bruder (1997) ArticleTitleOsteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 64 295–312 Occurrence Handle1:CAS:528:DyaK2sXpt1Kqsw%3D%3D Occurrence Handle9027589
MR Forwood MB Bennett AR Blowers RL Nadorfi (1998) ArticleTitleModification of the in vivo four-point loading model for studying mechanically induced bone adaptation. Bone 23 307–310 Occurrence Handle10.1016/S8756-3282(98)00090-8 Occurrence Handle1:STN:280:DyaK1cvgsleksQ%3D%3D Occurrence Handle9737355
A Sabokbar PJ Millett B Myer N Rushton (1994) ArticleTitleA rapid, quantitative assay for measuring alkaline phosphatase activity in osteoblastic cells in vitro. Bone Miner 27 57–67 Occurrence Handle1:CAS:528:DyaK2MXhsVSkt78%3D Occurrence Handle7849547
I Martin M Jakob D Schafer W Dick G Spagnoli et al. (2001) ArticleTitleQuantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints. Osteoarthritis Cartilage 9 112–118 Occurrence Handle10.1053/joca.2000.0366 Occurrence Handle1:STN:280:DC%2BD3M3lvFGntQ%3D%3D Occurrence Handle11237658
N Sato Y Takahashi S Asano (0000) ArticleTitlePreferential usage of bone-type leader sequence for the transcripts of liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes. Blood 83 1093–1994
S Pri-Chen S Pitaru F Lokiec N Savion (1998) ArticleTitleBasic fibroblastic growth factor enhances the growth and expression of the osteogenic phenotpe of dexamethasone-treated human bone marrow-derived bone-like cells in culture. Bone 23 111–117 Occurrence Handle10.1016/S8756-3282(98)00087-8 Occurrence Handle1:CAS:528:DyaK1cXlsVKgtbk%3D Occurrence Handle9701469
EA Botchwey SR Pollack EM Levine CT Laurencin (2001) ArticleTitleBone tissue engineering in a rotating bioreactor using a microcarrier matrix system. J Biomed Mater Res 55 242–253 Occurrence Handle10.1002/1097-4636(200105)55:2<242::AID-JBM1011>3.3.CO;2-4 Occurrence Handle1:CAS:528:DC%2BD3MXhs1OmtrY%3D Occurrence Handle11255176
PV Bodine SK Vernon BS Komm (1996) ArticleTitleEstablishment and hormonal regulation of a conditionally transformed preosteocytic cell line from adult human bone. Endocrinology 137 4592–4604 Occurrence Handle1:CAS:528:DyaK28Xms1Cqt7c%3D Occurrence Handle8895322
CH Turner I Owan T Alvey J Hulman JM Hock (1998) ArticleTitleRecruitment and proliferative responses of osteoblasts after mechanical loading in vivo determined using sustained-release bromodeoxyuridine. Bone 22 463–469 Occurrence Handle10.1016/S8756-3282(98)00041-6 Occurrence Handle1:STN:280:DyaK1c3mtFCjtA%3D%3D Occurrence Handle9600779
PJ Kostenuik BP Halloran ER Morey-Holton DD Bikle (1997) ArticleTitleSkeletal unloading inhibits the in vitro proliferation and differentiation of rat osteoprogenitor cells. Am J Physiol 273 1133–1139
R Zhang SC Supowit GL Klein Z Lu MD Christensen et al. (1995) ArticleTitleRat tail suspension reduces messenger RNA level for growth factors and osteopontin and decreases the osteoblastic differentiation of bone marrow stromal cells. J Bone Miner Res 10 415–423 Occurrence Handle1:CAS:528:DyaK2MXmvVWnsLo%3D Occurrence Handle7785463
S Keila S Pitaru A Grosskopf M Weinreb (1994) ArticleTitleBone marrow from mechanically unloaded rat bones expresses reduced osteogenic capacity in vitro. J Bone Miner Res 9 321–327 Occurrence Handle1:STN:280:ByuB2cbksVY%3D Occurrence Handle8191925
DM Raab-Cullen MP Akhter DB Kimmel RR Recker (1994) ArticleTitlePeriosteal bone formation stimulated by externally induced bending strains. J Bone Miner Res 9 1143–1152 Occurrence Handle1:STN:280:ByqD28jgtFc%3D Occurrence Handle7976496
CH Turner MR Forwood MW Otter (1994) ArticleTitleMechanotransduction in bone: do bone cells act as sensors of fluid flow? FASEB J 8 875–878 Occurrence Handle1:STN:280:ByuA2M%2FhvVY%3D Occurrence Handle8070637
AG Robling DB Burr CH Turner (2001) ArticleTitleRecovery periods restore mechanosensitivity to dynamically loaded bone. J Exp Biol 204 3389–3399
YF Hsieh T Wang CH Turner (1999) ArticleTitleViscoelastic response of the rat loading model: implications for studies of strain-adaptive bone formation. Bone 25 379–382 Occurrence Handle10.1016/S8756-3282(99)00181-7 Occurrence Handle1:STN:280:DyaK1Mvitlegtw%3D%3D Occurrence Handle10495144
HM Frost (1987) ArticleTitleBone “mass” and the “mechanostat”: a proposal. Anat Rec 219 1–9 Occurrence Handle1:STN:280:BieD2srhslw%3D Occurrence Handle3688455
Y Umemura T Ishiko T Yamauchi M Kurono S Mashiko (1997) ArticleTitleFive jumps per day increase bone mass and breaking force in rats. J Bone Miner Res 12 1480–1485 Occurrence Handle1:STN:280:ByiH3s3ovVE%3D Occurrence Handle9286765
LF Cooper CT Harris SP Bruder R Kowalski S Kadiyala (2001) ArticleTitleIncipient analysis of mesenchymal stem-cell-derived osteogenesis. J Dent Res 80 314–320 Occurrence Handle1:CAS:528:DC%2BD3MXivVOmt70%3D Occurrence Handle11269722
JE Aubin F Liu L Malaval AK Gupta (1995) ArticleTitleOsteoblast and chondroblast differentiation. Bone 17 77S–83S Occurrence Handle1:CAS:528:DyaK2MXns1OgsLc%3D Occurrence Handle8579903
J Chen K Singh BB Mukherjee J Sodek (1993) ArticleTitleDevelopmental expression of osteopontin (OPN) mRNA in rat tissues: evidence for a role for OPN in bone formation and resorption. Matrix 13 113–123 Occurrence Handle1:CAS:528:DyaK3sXhs1GrtLc%3D Occurrence Handle8492741
RS Carvalho A Bumann JL Schaffer LC Gerstenfeld (2002) ArticleTitlePredominant integrin ligands expressed by osteoblasts show preferential regulation in response to both cell adhesion and mechanical perturbation. J Cell Biochem 84 497–508 Occurrence Handle10.1002/jcb.10031.abs Occurrence Handle1:STN:280:DC%2BD38%2FosFClsw%3D%3D Occurrence Handle11813255
JN Beresford CJ Joyner C Devlin JT Triffitt (1994) ArticleTitleThe effects of dexamethasone and 1,25-dihydroxyvitamin D3 on osteogenic differentiation of human marrow stromal cells in vitro. Arch Oral Biol 39 941–947 Occurrence Handle1:CAS:528:DyaK2MXjs12ks70%3D Occurrence Handle7695507
O Frank M Heim M Jakob A Barbero D Schafer et al. (2002) ArticleTitleReal-time quantitative RT-PCR analysis of human bone marrow stromal cells during osteogenic differentiation in vitro. J Cell Biochem 85 737–746 Occurrence Handle10.1002/jcb.10174 Occurrence Handle1:CAS:528:DC%2BD38Xjs1Whs78%3D Occurrence Handle11968014
G Lisignoli N Zini G Remiddi A Piacentini A Puggioli et al. (2001) ArticleTitleBasic fibroblast growth factor enhances in vitro mineralization of rat bone marrow stromal cells grown on non-woven hyaluronic acid based polymer scaffold. Biomaterials 22 2095–2105 Occurrence Handle10.1016/S0142-9612(00)00398-7 Occurrence Handle1:CAS:528:DC%2BD3MXlt1Kmt7Y%3D Occurrence Handle11432589
S Ozawa S Kasugai (1996) ArticleTitleEvaluation of implant materials (hydroxyapatite, glass-ceramics, titanium) in rat bone marrow stromal cell culture. Biomaterials 17 23–29 Occurrence Handle10.1016/0142-9612(96)80751-4 Occurrence Handle1:CAS:528:DyaK28XhvFyjtw%3D%3D Occurrence Handle8962943
Q Qiu M Sayer M Kawaja X Shen JE Davies (1998) ArticleTitleAttachment, morphology, and protein expression of rat marrow stromal cells cultured on charged substrate surfaces. J Biomed Mater Res 42 117–127
J Becerra JA Andrades DC Ertl N Sorgente ME Nimni (1996) ArticleTitleDemineralized bone matrix mediates differentiation of bone marrow stromal cells in vitro, effect of age of cell donor. J Bone Miner Res 11 1703–1714 Occurrence Handle1:CAS:528:DyaK28XnsV2js7c%3D Occurrence Handle8915778
NK Harakas (1984) ArticleTitleDemineralized bone-matrix-induced osteogenesis. Clin Orthop 188 239–251 Occurrence Handle6380863
MR Urist (1965) ArticleTitleBone formation by autoinduction. Science 150 893–899 Occurrence Handle1:STN:280:CCmD3Mbjsl0%3D Occurrence Handle5319761
MR Urist RF DeLange GA Finerman (1983) ArticleTitleBone cell differentiation and growth factors. Science 220 680–686 Occurrence Handle1:CAS:528:DyaL3sXktlKgsLc%3D Occurrence Handle6403986
E Solheim (1998) ArticleTitleOsteoinduction by demineralized bone. Int Orthop 22 335–342 Occurrence Handle1:STN:280:DyaK1M7htleksg%3D%3D Occurrence Handle9914941
JB Lian GS Stein (1992) ArticleTitleConcepts of osteoblast growth and differentiation: basis for modulation of bone cell development and tissue formation. Crit Rev Oral Biol Med 3 269–305 Occurrence Handle1:STN:280:By2B3sbmtFM%3D Occurrence Handle1571474
LV Harter KA Hruska RL Duncan (1995) ArticleTitleHuman osteoblast-like cells respond to mechanical stain with increased bone matrix protein production independent of hormonal regulation. Endocrinology 136 528–535 Occurrence Handle1:CAS:528:DyaK2MXjtleitLw%3D Occurrence Handle7530647
D Kaspar W Seidl C Neidlinger-Wilke A Ignatius L Claes (2000) ArticleTitleDynamic cell stretching increases human osteoblast proliferation and CICP synthesis but decreases osteocalcin synthesis and alkaline phosphatase activity. J Biomech 33 45–51 Occurrence Handle10.1016/S0021-9290(99)00171-2 Occurrence Handle1:STN:280:DC%2BD3c%2FnsFKjug%3D%3D Occurrence Handle10609517
CH Turner FM Pavalko (1998) ArticleTitleMechanotransduction and functional response of the skeleton to physical stress: the mechanisms and mechanics of bone adaptation. J Orthop Sci 3 346–355 Occurrence Handle10.1007/s007760050064 Occurrence Handle1:STN:280:DyaK1M%2FjtVOltw%3D%3D Occurrence Handle9811988
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Mauney, J.R., Sjostorm, S., Blumberg, J. et al. Mechanical Stimulation Promotes Osteogenic Differentiation of Human Bone Marrow Stromal Cells on 3-D Partially Demineralized Bone Scaffolds In Vitro . Calcif Tissue Int 74, 458–468 (2004). https://doi.org/10.1007/s00223-003-0104-7
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DOI: https://doi.org/10.1007/s00223-003-0104-7