Strontium substitution in apatitic CaP cements effectively attenuates osteoclastic resorption but does not inhibit osteoclastogenesis

Schumacher, Matthias; Wagner, Alena-Svenja; Kokesch-Himmelreich, Julia; Bernhardt, Anne; Rohnke, Marcus; Wenisch, Sabine; Gelinsky, Michael

doi:10.1016/j.actbio.2016.04.016

Cited by 76 publications

(56 citation statements)

References 51 publications

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“…Besides this effect, strontium is also known for its attenuating effect on cellular bone resorption by osteoclasts. Recent studies by our group revealed that strontium concentrations to reduce the cellular resorption are most effective between 0.01 and 1 mM . Consistent with this effect, the histomorphometric analysis showed a reduced amount of osteoclasts and a slightly increased number of osteoblasts in groups with strontium‐modified scaffolds—these effects were not significant though.…”

Section: Discussionsupporting

confidence: 63%

“…Depending on the experimental design, different strontium concentrations have been shown to have a favorable influence on new bone formation in vitro . The most effective concentrations for bone‐forming cells are between 0.001 and 1 mM and between 0.01 and 1 mM for the attenuation of bone‐resorbing cells . In earlier studies, we showed that the scaffolds strontium release lies well within that range.…”

Section: Discussionmentioning

confidence: 60%

“…MCM has recently shown by Quade et al to be easily modified with strontium by substituting calcium with strontium in the mineralization batch, leading to a shift of the mineral phase from nanocrystalline hydroxyapatite (Sr0) over poorly crystalline Sr‐rich phases toward a mixed mineral phase (Sr100), consisting of an amorphous strontium phosphate (identified as Collin's salt, Sr 6 H 3 (PO 4 ) 5 × 2 H 2 O, CS) and highly crystalline strontium hydroxyapatite (Sr 5 (PO 4 ) 3 OH, SrHA) . During 28 days of immersion in vitro, the scaffolds revealed a sustained Sr 2+ release, whereby the released doses lay in the range reported to be suitable to exploit the dual effect of strontium by simultaneously promoting cell proliferation and osteogenic differentiation as well as inhibiting the osteoclastic bone resorption without impairing the osteoclastogenesis …”

Section: Introductionmentioning

confidence: 99%

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Strontium enhances BMP‐2 mediated bone regeneration in a femoral murine bone defect model

et al. 2019

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The application of strontium is one option for the clinical treatment of osteoporosis—a disease characterized by reduced bone density and quality—in order to reduce the risk of vertebral and nonvertebral fractures. Unlike other drugs used in osteoporosis therapy, strontium shows a dual effect on bone metabolism by attenuating cellular resorption and simultaneously enhancing new bone tissue formation. Current concerns regarding the systemic application of highly dosed strontium ranelate led to the development of strontium‐modified scaffolds based on mineralized collagen (MCM) capable to release biologically active Sr2+ ions directly at the fracture site. In this study, we investigated the regenerative potential of these scaffolds. For in vitro investigations, human mesenchymal stromal cells were cultivated on the scaffolds for 21 days (w/ and w/o osteogenic supplements). Biochemical analysis revealed a significant promoting effect on proliferation rate and osteogenic differentiation on strontium‐modified scaffolds. In vivo, scaffolds were implanted in a murine segmental bone defect model—partly additionally functionalized with the osteogenic growth factor bone morphogenetic protein 2 (BMP‐2). After 6 weeks, bridging calluses were obtained in BMP‐2 functionalized scaffolds; the quality of the newly formed bone tissue by means of morphological scores was clearly enhanced in strontium‐modified scaffolds. Histological analysis revealed increased numbers of osteoblasts and blood vessels, decreased numbers of osteoclasts, and significantly enhanced mechanical properties. These results indicate that the combined release of Sr2+ ions and BMP‐2 from the biomimetic scaffolds is a promising strategy to enhance bone regeneration, especially in patients suffering from osteoporosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:174–182, 2020.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

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Strontium enhances BMP‐2 mediated bone regeneration in a femoral murine bone defect model

et al. 2019

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“…However, only few studies have used CAII activity, instead of its mRNA expression, to analyse osteoclast formation and activity (Bernhardt et al, 2015;Detsch et al, 2010;Detsch and Boccaccini, 2015;Schumacher et al, 2016). The present study is the first to correlate CAII activity with osteoclastic resorption.…”

Section: Osteoclast-specific Enzyme Activities In Vitromentioning

confidence: 68%

Relevance of osteoclast-specific enzyme activities in cell-based in vitro resorption assays

Bernhardt

Koperski²,

Schumacher³

et al. 2017

eCM

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Cell-based in vitro resorption assays are an important tool to simulate the in vivo biodegradation of resorbable bone graft materials and to predict their clinical performance. The present study analyses the activity of osteoclastspecific enzymes as potential surrogate measures for classical pit assay, which is not applicable on irregular structured materials. Osteoclasts derived from human peripheral blood mononuclear cells were cultivated on different surfaces: calcium phosphate bone cements (CPC), dentin discs, osteoblast-derived extracellular matrix (ECM) and tissue culture polystyrene as control. Pit formation on the resorbable materials was investigated and correlated with the activity of tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (CAII) and cathepsin K (CTSK). Furthermore, the relation between intra-and extracellular enzyme activities was examined for TRAP and CTSK during resorption of the different materials. Resorbed area of CPC correlated with intracellular TRAP activity and intracellular CAII activity. Highest resorption was detected at around pH 7.2. Resorbed area on dentin correlated with the extracellular CTSK activity and extracellular TRAP activity and was maximal at around pH 6.8. Osteoclasts cultivated on cell-derived mineralised ECM showed a good correlation between both extracellular TRAP and CTSK activity and the release of calcium ions. Based on these data a different regulation of TRAP and CTSK secretion is hypothesised for the resorption of inorganic calcium phosphate compared to the resorption of collagenous mineralised matrix.

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“…The samples were then imaged using a TPLSM (Olympus FV1000MPE, Olympus GmbH, Hamburg, Germany). To visualize the sample surface after the cultivation, the RAW cells were removed after 14 days as described earlier . Briefly, samples were immersed in 1% Triton X‐100/PBS for 50 min on a shaker (50 rpm) and a subsequent ultrasonic treatment in deionized water for 4 min.…”

Section: Methodsmentioning

confidence: 99%

Periodic microstructures on bioactive glass surfaces enhance osteogenic differentiation of human mesenchymal stromal cells and promote osteoclastogenesis in vitro

Höner

Lauria

Dabhi

et al. 2018

J Biomedical Materials Res

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Bioactive glasses (BG) are known for their ability to bond to hard and soft tissues. We hypothesized that the stimulation of bone remodeling, including cellular bone forming and bone resorbing processes, can be increased by applying periodic microstructures on the glass surfaces in vitro. To test our hypothesis, two different BG (45S5 and 13-93) were microstructured in a groove-and-ridge pattern of different sizes by a novel casting process and tested in cell culture experiments using human mesenchymal stromal cells (hMSCs) and RAW 264.7 cells. The microstructures induced contact guidance of hMSCs and increased osteogenic marker gene expression of the stem cells, compared to non-structured glass surfaces as verified by ELISA and quantitative real-time PCR (qPCR) analyses. Furthermore, the structures stimulated the differentiation of RAW cells to osteoclast-like cells confirmed by TRAP gene expression and their resorption activity causing visible resorption lacunae. Our results demonstrate that periodically microstructured BG (especially 45S5) might improve the osteogenic differentiation of hMSCs and influence the activity of material resorbing cells in vitro. Hence, microstructuring of BG could enhance the remodeling process of bone substitutes critical for the formation of new bone tissue in vivo and thus be used to trigger bone remodeling kinetics in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1965-1978, 2018.

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Strontium substitution in apatitic CaP cements effectively attenuates osteoclastic resorption but does not inhibit osteoclastogenesis

Cited by 76 publications

References 51 publications

Strontium enhances BMP‐2 mediated bone regeneration in a femoral murine bone defect model

Strontium enhances BMP‐2 mediated bone regeneration in a femoral murine bone defect model

Relevance of osteoclast-specific enzyme activities in cell-based in vitro resorption assays

Periodic microstructures on bioactive glass surfaces enhance osteogenic differentiation of human mesenchymal stromal cells and promote osteoclastogenesis in vitro

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