Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation

Gentleman, Eileen; Swain, Robin J.; Evans, Nicholas D.; Boonrungsiman, Suwimon; Jell, Gavin; Ball, M.; Shean, Tamaryn A.V.; Oyen, Michelle L.; Porter, Alexandra E.; Stevens, Molly M.

doi:10.1038/nmat2505

Cited by 211 publications

(228 citation statements)

References 38 publications

(40 reference statements)

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“…The carbonate to phosphate ratios may not be in accordance with findings reported by various research groups [26,28,31,34]. However, the ratio is similar to the carbonate to phosphate ratio of native bone that was found to have a value of 3.84 ± 0.03.…”

Section: Univariate Peak Analysiscontrasting

confidence: 52%

Assessment of an osteoblast-like cell line as a model for human primary osteoblasts using Raman spectroscopy

McManus¹,

Bonnier²,

Burke³

et al. 2012

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Raman spectroscopy is employed to determine the suitability of the U20S osteoblast-like cell line for use as a model for human primary osteoblasts, with emphasis on the ability of these cell types to replicate their tissue of origin. It was found that both cell types demonstrated early stage mineral deposition that followed significantly different growth patterns. Analysis of the growth pattern and spectral data from primary cells revealed increasing bone quality ratios and a high crystallinity, consistent with previous reports. Conversely the investigation of the U20S osteoblast-like cell line provided evidence of dense multilayered mineralised regions that corresponded more closely to native bone in terms of its crystallinity and bone quality ratios. This finding contradicts previous reports on U20S osteoblast-like cells which have consistently described them as non-osteoinductive when cultured in various conditions on a number of substrates. This work demonstrates the successful application of Raman spectroscopy combined with biological and multivariate analysis for the investigation of osteoblast-like U20S cells and human primary osteoblasts, specifically with focus on the osteoinductive ability of the osteoblast-like cell line and the comparative differences in relation to the primary osteoblasts.

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Section: Univariate Peak Analysiscontrasting

confidence: 52%

Assessment of an osteoblast-like cell line as a model for human primary osteoblasts using Raman spectroscopy

McManus¹,

Bonnier²,

Burke³

et al. 2012

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“…We have previously demonstrated by multivariate analyses of microRaman spectra that such live, unprocessed nodules possess important characteristics of native bone, including the presence of a complex combination of mineral and matrix environments (14). Mineralized nodules formed from osteoblasts, when prepared by chemical fixation and analyzed by bright-field transmission electron microscopy (TEM), contained morphologically normal cells surrounded by a fibrous ECM (Fig.…”

Section: Resultsmentioning

confidence: 99%

The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation

Boonrungsiman¹,

Gentleman

Carzaniga

et al. 2012

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

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Mineralization is a ubiquitous process in the animal kingdom and is fundamental to human development and health. Dysfunctional or aberrant mineralization leads to a variety of medical problems, and so an understanding of these processes is essential to their mitigation. Osteoblasts create the nano-composite structure of bone by secreting a collagenous extracellular matrix (ECM) on which apatite crystals subsequently form. However, despite their requisite function in building bone and decades of observations describing intracellular calcium phosphate, the precise role osteoblasts play in mediating bone apatite formation remains largely unknown. To better understand the relationship between intracellular and extracellular mineralization, we combined a samplepreparation method that simultaneously preserved mineral, ions, and ECM with nano-analytical electron microscopy techniques to examine osteoblasts in an in vitro model of bone formation. We identified calcium phosphate both within osteoblast mitochondrial granules and intracellular vesicles that transported material to the ECM. Moreover, we observed calcium-containing vesicles conjoining mitochondria, which also contained calcium, suggesting a storage and transport mechanism. Our observations further highlight the important relationship between intracellular calcium phosphate in osteoblasts and their role in mineralizing the ECM. These observations may have important implications in deciphering both how normal bone forms and in understanding pathological mineralization.biomineralization | crystallinity | mineral transport | electron energy-loss spectroscopy

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“…Once acquired, the Raman spectra were baseline corrected (rubber band, five iterations) so as to account for fluorescence, (10) and the following Raman parameters were calculated, as published elsewhere (2,11) : (1) The mineral/matrix ratio was expressed as the integrated areas of the v 1 PO 4 (930 to 980 cm À1 ) to the amide I (1620 to 1700 cm À1 ) bands and of Crosses indicate regions where Raman spectra were acquired. For this study, only spectra obtained between the two labels (denoted by black arrows) were processed.…”

Section: Bone Biopsiesmentioning

confidence: 99%

Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly Zoledronic acid

Gamsjaeger

Buchinger

Zwettler

et al. 2010

Journal of Bone and Mineral Research

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Zoledronic acid (ZOL), a third-generation aminobisphosphonate, showed pronounced antifracture efficacy in a phase III clinical trial [Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT)] when administered yearly (5-mg infusions of ZOL), producing significant reductions in morphometric vertebral, clinical vertebral, hip, and nonvertebral fractures by 70%, 77%, 41%, and 25%, respectively, over a 3-year period. The purpose of this study was to analyze the biopsies obtained during the HORIZON clinical trial (152 patients, 82 ZOL and 70 placebo) by means of Raman microspectroscopy (a vibrational spectroscopic technique capable of analyzing undecalcified bone tissue with a spatial resolution of approximately 0.6 mm) to determine the effect of ZOL therapy on bone material properties (in particular mineral/matrix ratio, lamellar organization, carbonate and proteoglycan (based on spectral identification of glycosaminoglycan) content, and mineral maturity/crystallinity) at similar tissue age (based on the presence of tetracycline double labels). The results indicated that while ZOL administration increased the mineral/ matrix ratio compared with placebo, it also resulted in mineral crystallites with a quality profile (based on carbonate content and maturity/crystallinity characteristics) of younger (with respect to tissue age) bone. Since the comparisons between ZOL-and placebotreated patients were performed at similar tissue age at actively forming bone surfaces, these results suggest that ZOL may be exerting an effect on bone matrix formation in addition to its well-established antiresorptive effect, thereby contributing to its antifracture efficacy. ß

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Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation

Cited by 211 publications

References 38 publications

Assessment of an osteoblast-like cell line as a model for human primary osteoblasts using Raman spectroscopy

Assessment of an osteoblast-like cell line as a model for human primary osteoblasts using Raman spectroscopy

The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation

Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly Zoledronic acid

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