A scaffold-free multicellular three-dimensional in vitro model of osteogenesis.


:In vitro models of osteogenesis are essential for investigating bone biology and the effects of pharmaceutical, chemical, and physical cues on bone formation. Osteogenesis takes place in a complex three-dimensional (3D) environment with cells from both mesenchymal and hematopoietic origins. Existing in vitro models of osteogenesis include two-dimensional (2D) single type cell monolayers and 3D cultures. However, an in vitro scaffold-free multicellular 3D model of osteogenesis is missing. We hypothesized that the self-inductive ossification capacity of bone marrow tissue can be harnessed in vitro and employed as a scaffold-free multicellular 3D model of osteogenesis. Therefore, rat bone marrow tissue was cultured for 28 days in three settings: 2D monolayer, 3D homogenized pellet, and 3D organotypic explant. The ossification potential of marrow in each condition was quantified by micro-computed tomography. The 3D organotypic marrow explant culture resulted in the greatest level of ossification with plate-like bone formations (up to 5 mm in diameter and 0.24 mm in thickness). To evaluate the mimicry of the organotypic marrow explants to newly forming native bone tissue, detailed compositional and morphological analyses were performed, including characterization of the ossified matrix by histochemistry, immunohistochemistry, Raman microspectroscopy, energy dispersive X-ray spectroscopy, backscattered electron microscopy, and micromechanical tests. The results indicated that the 3D organotypic marrow explant culture model mimics newly forming native bone tissue in terms of the characteristics studied. Therefore, this platform holds significant potential to be used as a model of osteogenesis, offering an alternative to in vitro monolayer cultures and in vivo animal models.


Calcif Tissue Int


Gurkan UA,Kishore V,Condon KW,Bellido TM,Akkus O




Has Abstract


2011-05-01 00:00:00












  • The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2.

    abstract::Mechanical forces applied to cultured bone cells induce the production of cAMP via stimulation of the formation of prostaglandin E2 (PGE2) and its release into the medium, resulting in stimulation of adenylate cyclase. In this paper we show that either the antibiotic gentamycin (100 micrograms/ml) or antiphospholipid ...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Binderman I,Zor U,Kaye AM,Shimshoni Z,Harell A,Sömjen D

    更新日期:1988-04-01 00:00:00

  • Bone mineral density and bone turnover in patients with knee osteoarthritis compared with generalized osteoarthritis.

    abstract::The aim of this study was to investigate bone mineral density (BMD) and bone turnover in patients with primary knee osteoarthritis (KOA) and to compare them with generalized OA (GOA) and nonGOA patients. A total of 88 postmenopausal primary KOA patients were studied. OA was graded by using knee radiographs. BMD of the...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Naitou K,Kushida K,Takahashi M,Ohishi T,Inoue T

    更新日期:2000-05-01 00:00:00

  • Effects of parathyroid hormone on odontogenesis of the mouse embryonic molar tooth in vitro.

    abstract::Mandibular first molars of 17-day-old mouse embryos were cultured in vitro to examine the histological effects of various concentrations of parathyroid hormone (PTH) on odontogenesis of the molars. PTH did not affect the cytodifferentiation of mesenchymal cells into preodontoblasts but inhibited that of preodontoblast...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Sakakura Y

    更新日期:1987-01-01 00:00:00

  • Rapid establishment of chemical and mechanical properties during lamellar bone formation.

    abstract::The development of prophylaxes and treatments of bone diseases that can effectively increase the strength of bone as a structure necessitates a better understanding of the time course by which chemical properties define the stiffness of the material during primary and secondary mineralization. It was hypothesized that...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Busa B,Miller LM,Rubin CT,Qin YX,Judex S

    更新日期:2005-12-01 00:00:00

  • The relation between trabecular bone strength and bone mineral density assessed by dual photon and dual energy X-ray absorptiometry in the proximal tibia.

    abstract::The feasibility of two noninvasive methods [dual photon absorptiometry (DPA) and dual energy X-ray absorptiometry (DXA)] for prediction in vivo of local variations of trabecular bone strength within the proximal tibia was evaluated in 14 cadaveric knees. Trabecular bone strength was measured using an osteopenetrometer...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Petersen MM,Jensen NC,Gehrchen PM,Nielsen PK,Nielsen PT

    更新日期:1996-10-01 00:00:00

  • Transforming growth factor beta 1-induced cellular heterogeneity in the periosteum of rat parietal bones.

    abstract::We examined the osteogenesis process in transforming growth factor beta 1 (TGF-beta 1)-treated neonatal and adult rats, aiming to investigate the age difference in the effect of TGF-beta 1 on mesenchymal cell differentiation. Recombinant human (rh) TGF-beta 1 (20 and 200 ng) was injected onto the outer periostea of th...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Taniguchi Y,Tanaka T,Gotoh K,Satoh R,Inazu M

    更新日期:1993-08-01 00:00:00

  • Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament.

    abstract::Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Mechanical stress, which acts on the posterior ligaments, is thought to be an important factor in the progression of OPLL. To clarify this mechanism, we investigated the effects o...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Iwasaki K,Furukawa KI,Tanno M,Kusumi T,Ueyama K,Tanaka M,Kudo H,Toh S,Harata S,Motomura S

    更新日期:2004-05-01 00:00:00

  • Bone Matrix Composition Following PTH Treatment is Not Dependent on Sclerostin Status.

    abstract::Sclerostin and parathyroid hormones are strong negative and positive regulators of bone formation, respectively. The anabolic response induced by intermittent (iPTH) treatment is sclerostin status-dependent. However, the interaction between sclerostin and iPTH at the matrix level is unknown. The goal of the current st...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Ross RD,Mashiatulla M,Robling AG,Miller LM,Sumner DR

    更新日期:2016-02-01 00:00:00

  • Dual X-ray absorptiometry: clinical evaluation of a new cone-beam system.

    abstract::The DMS Lexxos is the first cone-beam dual X-ray absorptiometry (DXA) system capable of performing bone mineral density (BMD) measurements of the spine and hip. By using a two-dimensional (2-D) detector array rather than the linear array used with conventional fan-beam DXA systems, image acquisition time on Lexxos is ...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Blake GM,Knapp KM,Fogelman I

    更新日期:2005-02-01 00:00:00

  • A pediatric bone mass scan has poor ability to predict adult bone mass: a 28-year prospective study in 214 children.

    abstract::As the correlation of bone mass from childhood to adulthood is unclear, we conducted a long-term prospective observational study to determine if a pediatric bone mass scan could predict adult bone mass. We measured cortical bone mineral content (BMC [g]), bone mineral density (BMD [g/cm(2)]), and bone width (cm) in th...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Buttazzoni C,Rosengren BE,Tveit M,Landin L,Nilsson JÅ,Karlsson MK

    更新日期:2014-02-01 00:00:00

  • Comparison of growth retarding effects induced by two different glucocorticoids in prepubertal sick children: an interim long-term analysis.

    abstract::The low interference with growth expected in child for a cortisol analogue, deflazacort (DFZ), prompted us to verify if DFZ could affect growth less than prednisone (PDN). An interim analysis relative to 27 girls and 38 boys (out of 100 expected) aged 3-12 yrs, after a median period of 14 mo.s is reported. Children wi...

    journal_title:Calcified tissue international

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Aicardi G,Milani S,Imbimbo B,Vignolo M,Di Battista E,Gusmano R,Terragna A,Cordone G,Cottafava F,Coppo R

    更新日期:1991-04-01 00:00:00

  • Correlation among plasma osteocalcin, growth hormone, and somatomedin C in acromegaly.

    abstract::Plasma osteocalcin (BGP), growth hormone (GH), and somatomedin C(SmC) were measured in 12 patients with acromegaly [7 clinically active (aA), 5 cured (cA)] and 9 control subjects (C). Basal plasma values for the three parameters were higher in aA than in C and in cA. No significant difference was found between cA and ...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: de la Piedra C,Larrañaga J,Castro N,Horcajada C,Rapado A,Herrera Pombo JL,Carbó E

    更新日期:1988-07-01 00:00:00

  • Urinary 3H-tetracycline and pyridinium crosslinks differ in their response to calcium restriction in mature and aged rats.

    abstract::The aim of this study was to evaluate bone resorption (BR) in rats by two methods: chronic 3H-tetracycline labeling (3HTC) and pyridinium crosslink excretion (PYDX), and compare the sensitivity of these markers in two age groups. Female Sprague-Dawley rats at 12-29 weeks of age ("mature", n = 12) and at 40-57 weeks of...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Talbott SM,Chowdhury H,Shapses SA

    更新日期:1999-04-01 00:00:00

  • Changes in proline synthetic and degradative enzymes during matrix-induced cartilage and bone formation.

    abstract::Proline biosynthetic and degradative enzymes are unevenly distributed in differentiated mammalian tissues. Activities of the synthetic enzymes are relatively high in collagenous tissues, whereas activities of the degradative enzymes are high in noncollagenous tissues. In order to further characterize tissue-specific p...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Smith RJ,Reddi AH,Phang JM

    更新日期:1979-07-03 00:00:00

  • Vitamin D insufficiency in Greenlanders on a westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes.

    abstract::We studied the influence of age, gender, latitude, season, diet and ethnicity on plasma 25-hydroxyvitamin D 25 OHD, PTH, 1,25-dihydroxyvitamin D, vitamin D-binding protein, bone-specific alkaline phosphatase, and osteocalcin levels in 46 Greenlanders living in Nuuk (64 degrees N) on a traditional fare (group A), 45 Gr...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Rejnmark L,Jørgensen ME,Pedersen MB,Hansen JC,Heickendorff L,Lauridsen AL,Mulvad G,Siggaard C,Skjoldborg H,Sørensen TB,Pedersen EB,Mosekilde L

    更新日期:2004-03-01 00:00:00

  • Familial hypocalciuric hypercalcemia in Israel: a preliminary report.

    abstract::Familial hypocalciuric hypercalcemia (FHH) is often considered in the differential diagnosis of hyperparathyroidism, but is rarely diagnosed. So far, FHH has not been documented in Israel. This report presents preliminary evidence for the occurrence of FHH in Israel. ...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Liel Y,Arie R,Vered I

    更新日期:1997-07-01 00:00:00

  • Adiponectin and peak bone mass in men: a cross-sectional, population-based study.

    abstract::Adiponectin, a protein classically known to be secreted by adipocytes, is also secreted by bone-forming cells. Results of previous studies have been contradictory as to whether serum adiponectin and bone mineral density (BMD) are associated. The aim of this study was to investigate a possible association between serum...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Frost M,Abrahamsen B,Nielsen TL,Frystyk J,Flyvbjerg A,Hagen C,Andersen M,Brixen K

    更新日期:2010-07-01 00:00:00

  • Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity.

    abstract::This study aimed to investigate the effects of recombinant human bone morphogenetic protein (rhBMP-7) on human cancellous bone grafts (BGs) while differentiating between anabolic and catabolic events. Human BGs alone or supplemented with rhBMP-7 were harvested 14 weeks after subcutaneous implantation into NOD/Scid mic...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Lahr CA,Wagner F,Shafiee A,Rudert M,Hutmacher DW,Holzapfel BM

    更新日期:2019-09-01 00:00:00

  • Effect of periosteal stripping on cortical bone perfusion: a laser doppler study in sheep.

    abstract::The goals of internal fixation are an accurate reduction and stable fixation in the presence of adequate bony vascularity. This can be achieved by a variety of means including plate fixation. A certain amount of periosteal stripping is necessary for proper open reduction of a fracture and for proper plate application....

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Kowalski MJ,Schemitsch EH,Kregor PJ,Senft D,Swiontkowski MF

    更新日期:1996-07-01 00:00:00

  • Correlated physiochemical and age changes in embryonic bovine enamel.

    abstract::Whole enamel scrapings from unerupted teeth of embryonic calves have been separated into fractions of varying density by stepwise centrifugation in bromoform-toluene mixtures of increasing specific gravity. Partition of enamel in this manner yields individual fractions of increasing mineral phase age and maturation. W...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Landis WJ,Navarro M

    更新日期:1983-01-01 00:00:00

  • The nitric oxide donor sodium nitroprusside inhibits mineralization in ATDC5 cells.

    abstract::The aim of this study was to test whether the nitric oxide (NO) donor sodium nitroprusside (SNP) has an effect on mineralization in ATDC5 cells. Mineralization in ATDC5 cell culture was induced by addition of beta-glycerophosphate or inorganic phosphate, visualized by staining precipitated calcium with an alizarin red...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Huitema LF,Vaandrager AB,van Weeren PR,Barneveld A,Helms JB,van de Lest CH

    更新日期:2006-03-01 00:00:00

  • Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures.

    abstract::It has been suggested that oxidative stress is associated with the pathogenesis of osteoporosis. The objective of this study was to explore the association between a marker of oxidative stress and either bone turnover markers or bone mineral density (BMD) in postmenopausal women. In addition, the effects of oxidative ...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Baek KH,Oh KW,Lee WY,Lee SS,Kim MK,Kwon HS,Rhee EJ,Han JH,Song KH,Cha BY,Lee KW,Kang MI

    更新日期:2010-09-01 00:00:00

  • Osteoarthritis: Current Molecular Biomarkers and the Way Forward.

    abstract::The ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeostasis and/or joint s...

    journal_title:Calcified tissue international

    pub_type: 杂志文章,评审


    authors: Kraus VB,Karsdal MA

    更新日期:2020-05-04 00:00:00

  • Associations Between Objectively Measured Physical Activity, Body Composition and Sarcopenia: Findings from the Hertfordshire Sarcopenia Study (HSS).

    abstract::Regular physical activity (PA) is associated with reduced risk of the development and progression of musculoskeletal, metabolic and vascular disease. However, PA declines with age and this can contribute to multiple adverse outcomes. The aims of this study were to describe the relationship between accelerometer-determ...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Westbury LD,Dodds RM,Syddall HE,Baczynska AM,Shaw SC,Dennison EM,Roberts HC,Sayer AA,Cooper C,Patel HP

    更新日期:2018-09-01 00:00:00

  • Involvement of insulin-like growth factor I in development of ossification of the posterior longitudinal ligament of the spine.

    abstract::In order to investigate the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) of the spine, we examined the distribution of insulin-like growth factor I (IGF-I) in the posterior longitudinal ligaments of OPLL patients, and analyzed the effects of IGF-I on the cultured spinal ligament cells. Fo...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Goto K,Yamazaki M,Tagawa M,Goto S,Kon T,Moriya H,Fujimura S

    更新日期:1998-02-01 00:00:00

  • Quantitative assessment of experimental fracture repair by peripheral computed tomography.

    abstract::An experimental fracture model was used to assess bone mineral density at the fracture site by peripheral computed tomography and to compare the model with biomechanical, histological, and radiographic methods for the quantification of the fracture repair process. Transverse osteotomies in the mid-diaphysis of 28 tibi...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Augat P,Merk J,Genant HK,Claes L

    更新日期:1997-02-01 00:00:00

  • Differential response in alveolar bone osteoclasts residing at two different bone sites.

    abstract::Using a histochemical method for demonstrating acid phosphatase activity, we have studied osteoclasts residing at two different bone sites in rat incisor alveolar bone, one at the endosteum and the other at the tooth socket, and compared the response of these osteoclasts to systemic changes. After 12 days of calcium (...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Liu CC,Baylink DJ

    更新日期:1984-03-01 00:00:00

  • Three-Dimensional Porous Gelapin-Simvastatin Scaffolds Promoted Bone Defect Healing in Rabbits.

    abstract::Treatment of large bone defects (LBDs) is technically demanding. Tissue engineering is an option. A bioactive graft may be produced by combining tissue scaffolds and healing promotive factors in order to accelerate bone repair. We investigated the role of Simvastatin (Sim)-embedded porous Gelapin (Gel) scaffold on exp...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Moshiri A,Shahrezaee M,Shekarchi B,Oryan A,Azma K

    更新日期:2015-06-01 00:00:00

  • Subregional DXA-derived vertebral bone mineral measures are stronger predictors of failure load in specimens with lower areal bone mineral density, compared to those with higher areal bone mineral density.

    abstract::Measurement of areal bone mineral density (aBMD) in intravertebral subregions may increase the diagnostic sensitivity of dual-energy X-ray absorptiometry (DXA)-derived parameters for vertebral fragility. This study investigated whether DXA-derived bone parameters in vertebral subregions were better predictors of verte...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Briggs AM,Perilli E,Codrington J,Reynolds KJ,Parkinson IH,Wark JD

    更新日期:2014-08-01 00:00:00

  • Expression patterns of Raf-1 suggest multiple roles in tooth development.

    abstract::Raf-1, the product of proto-oncogene c-raf-1, has key roles in the signal transduction pathways within the cell. The molecular mechanisms of tooth development in the mouse embryo are not known in detail. We examined the expression of Raf-1 during subsequent tooth development by immunohistochemical analysis. In mouse e...

    journal_title:Calcified tissue international

    pub_type: 杂志文章


    authors: Sunohara M,Tanzawa H,Kaneko Y,Fuse A,Sato K

    更新日期:1996-01-01 00:00:00