Maturation State Determines the Response of Osteogenic Cells to Surface Roughness and 1,25-Dihydroxyvitamin D3

Lohmann, Christoph H.; Bonewald, Lynda F.; Sisk, Marc A.; Sylvia, V. L.; Cochran, David L.; Dean, David D.; Boyan, Barbara D.; Schwartz, Zvi

doi:10.1359/jbmr.2000.15.6.1169

Cited by 141 publications

(108 citation statements)

References 34 publications

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“…This study supports other observations in our lab showing that alkaline phosphatase is regulated separately from osteocalcin [24]. Alkaline phosphatase activity is increased in osteoblast cultures prior to the onset of calcification, whereas osteocalcin synthesis occurs as calcification is initiated [18,23].…”

Section: Discussionsupporting

confidence: 92%

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Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast‐like cells

Boyan

Schwartz

Lohmann

et al. 2003

Journal Orthopaedic Research

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Implant surface morphology regulates osteoblast phenotypic expression. Osteoblast sensitivity to non-biologic surfaces suggests that native bone surface features may also affect osteoblast response. To test this, MG63 osteoblast-like cells were grown for 7 days on bovine cortical bone wafers pretreated with rat bone marrow osteoclasts for 0, 10 or 20 days. Response to osteoclast-treated surfaces was compared to the response of MG63 cells to titanium surfaces with smooth and rough microtopographies. Cell number, differentiation (alkaline phosphatase activity and osteocalcin levels), and local factors (PGE? and TGF-fi 1) were measured in confluent cultures. Compared to culture on plastic, cell number was reduced on all three types of bone wafers; this eflect was dosedependent with increasing resorption of the surface. Alkaline phosphatase specific activity was increased ( P < 0.05) on all three surfaces compared with plastic, but this increase was not dependent on resorption time, indicating this parameter was sensitive to the surface (bovine bone vs. plastic) but not to osteoclast-resorption. There was a direct correlation between the area of the bone surface resorbed and the amount of osteocalcin, TGF-PI and PGEz (R' = 0. 8025, 0.8689, 0.8896, respectively). With 20 days of osteoclast pretreatment, there was a 20-fold increase in osteocalcin over plastic and a 7-fold increase over cultures on untreated bone wafers. Similar increases were found for TGF-PI and PGEz. Thus, surface changes resulting from osteoclast pretreatment have a strong effect on osteoblast phenotypic expression, and suggest that microtopography may play a role.

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Section: Discussionsupporting

confidence: 92%

“…When MG63 human osteoblastlike osteosarcoma cells [5], fetal rat calvarial cells [24], or normal human osteoblast cells (NHOst) [25] are cultured on titanium disks with varying microtopographies, there is a roughness-dependent effect on phenotypic expression. As roughness increases, proliferation decreases.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast‐like cells

Boyan

Schwartz

Lohmann

et al. 2003

Journal Orthopaedic Research

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“…They are a well characterized osteoblastlike cell culture model for assessing responses to Ti surface microstructure (24, 51) and surface energy (28). Observations using MG63 cells have been confirmed by using normal human osteoblasts (52), normal mouse calvarial osteoblasts, fetal rat calvarial cells, and other osteoblast cell lines (53), and the results correlate with clinical performance in animals and humans (3-5, 7, 8).…”

Section: Resultsmentioning

confidence: 92%

Integrin α2β1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates

Olivares-Navarrete

Raz

Zhao

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Efforts to improve bone response to biomaterials have focused on ligands that bind ␣5␤1 integrins. However, antibodies to ␣5␤1 reduce osteoblast proliferation but do not affect differentiation when cells are grown on titanium (Ti). ␤1-silencing blocks the differentiation stimulus of Ti microtopography, suggesting that other ␤1 partners are important. Stably ␣2-silenced MG63 human osteoblast-like cells were used to test whether ␣2␤1 specifically mediates osteoblast response to Ti surface micron-scale structure and energy. WT and ␣2-silenced MG63 cells were cultured on tissue culture polystyrene (TCPS) and Ti disks with different surface microtopographies: machined pretreatment (PT) surfaces [mean peak to valley roughness (R a) < 0.02 m], PT surfaces that were grit-blasted and acid-etched (SLA; R a ‫؍‬ 4 m), and SLA with high surface energy (modSLA). Alkaline phosphatase (ALP), ␣2 and ␤1 mRNA, but not ␣5, ␣v, ␤3, type-I collagen, or osteocalcin, increased on SLA and modSLA at 6 days. ␣2 increased at 8 days on TCPS and PT, but remained unchanged on SLA and modSLA. ␣2-protein was reduced 70% in ␣2-siRNA cells, whereas ␣5-mRNA and protein were unaffected. ␣2-knockdown blocked surface-dependent increases in ␤1 and osteocalcin and decreases in cell number and increases in ALP and local factors typical of MG63 cells grown on SLA and modSLA [e.g., prostaglandin E 2, osteoprotegerin, latent and active TGF-␤1, and stimulatory effects of 1␣,25(OH)2D3 on these parameters]. This finding indicates that ␣2␤1 signaling is required for osteoblastic differentiation caused by Ti microstructure and surface energy, suggesting that conclusions based on cell behavior on TCPS are not predictive of behavior on other substrates or the mechanisms involved.␣-2 integrin siRNA ͉ MG63 human osteoblasts ͉ titanium surface roughness T itanium (Ti) and Ti alloys are commonly used as biomaterials because their surface properties provide a biocompatible interface with peri-implant tissues. Strategies for modifying the nature of this interface frequently involve changes to the surface, thereby affecting protein adsorption, cell-substrate interactions, and tissue development (1). A common modification has been to create micron-scale and submicron scale roughness. Preclinical and clinical studies (2-12) show that these surfaces support greater bone-to-implant contact than smooth surfaces.How surface microstructure promotes an osteogenic response is an important question, because bone-forming osteoblasts preferentially colonize bone surfaces that have been preconditioned by bone-resorbing osteoclasts (13), resulting in complex micron-scale and submicron-scale morphologies (14). In vitro experiments using model surfaces indicate that migration, growth, and colony morphology of rat bone marrow cells (15) and osteoblasts (16-18) are sensitive to microstructure. These observations suggest that structural elements can modulate the spatial organization of cells and their ECM.The topography of osteoclast resorption pits in bone can be modeled by using Ti subs...

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“…Nonetheless, Lohmann et al 35) showed -using three types of osteogenic cell lines -that osteoblastic cells responded in a differential manner to changes in surface roughness depending on their maturation state. In other words, the types and conditions of cells in the osteoblast lineage may affect proliferation responses to surface roughness.…”

Section: Discussionmentioning

confidence: 99%

Surface Properties and Biocompatibility of Acid-etched Titanium

et al. 2008

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The purpose of this study was to evaluate the effects of acid-etched titanium on the biological responses of osteoblast-like MC3T3-E1 cells. Four types of treatments (polishing, sandblasting, concentrated H2SO4 etching, and concentrated H2SO4 etching with vacuum firing) were carried out on the surfaces of commercially pure titanium (cpTi) disks. MC3T3-E1 cells were then cultured on the treated cpTi surfaces. Through surface roughness measurement and SEM analysis, it was found that the acid-etched surfaces showed higher roughness values than the sandblasted ones. Scanning electron microscope analysis showed that the cells on the disks treated with acid-etching and acid-etching with vacuum firing spread as well as the sandblasted ones. There were no significant differences in cell proliferation and collagen production on cpTi among the four different surface treatments. Based on the results of this study, it was concluded that etching with concentrated sulfuric acid was a simple and effective way to roughen the surface of titanium without compromising its biocompatibility.

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Maturation State Determines the Response of Osteogenic Cells to Surface Roughness and 1,25-Dihydroxyvitamin D3

Cited by 141 publications

References 34 publications

Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast‐like cells

Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast‐like cells

Integrin α2β1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates

Surface Properties and Biocompatibility of Acid-etched Titanium

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