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      Quantitative anatomy of the primary ossification center of the femoral shaft in human fetuses

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          Abstract

          Purpose

          Early clinical distinction of congenital defects in the femur is extremely important, as it determines the prognosis of the development of the lower limb. This study was performed to quantitatively examine the primary center of ossification in the femoral shaft with respect to its linear, planar, and volumetric parameters.

          Materials and methods

          Using methods of CT, digital-image analysis, and statistics, the size of the primary ossification center of the femoral shaft in 47 spontaneously aborted human fetuses aged 17–30 weeks was studied.

          Results

          With no sex and laterality differences, the best fit growth dynamics for femoral shaft ossification center was modelled by the following functions: y = 5.717 + 0.040 × (age) 2 ± 2.905 ( R 2 = 0.86) for its length, y = −3.579 + 0.368 × age ± 0.529 ( R 2 = 0.88) for its proximal transverse diameter, y = −1.105 + 0.187 × age ± 0.309 ( R 2 = 0.84) for its middle transverse diameter, y = −2.321 + 0.323 × age ± 0.558 ( R 2 = 0.83) for its distal transverse diameter, y = −50.306 + 0.308 × (age) 2 ± 18.289 ( R 2 = 0.90) for its projection surface area, and y = −91.458 + 0.390 × (age) 3 ± 92.146 ( R 2 = 0.88) for its volume.

          Conclusions

          The size of the femoral shaft ossification center displays neither sex nor laterality differences. The ossification center in the femoral shaft follows quadratic functions with respect to its length and projection surface area, linear functions with respect to its proximal, middle, and distal transverse diameters, and a cubic function with respect to its volume. The obtained morphometric data of the femoral shaft ossification center are considered normative for respective prenatal weeks and may be of relevance in both the estimation of fetal ages and the ultrasound diagnostics of congenital defects.

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          Most cited references21

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          S100A4: a novel negative regulator of mineralization and osteoblast differentiation.

          S100A4 is an intracellular calcium-binding protein expressed by osteoblastic cells. However, its roles in bone physiology are unknown. Because before matrix mineralization, its expression is markedly diminished, we hypothesized that S100A4 negatively regulates the mineralization process. In this study, we investigated the effects of the inhibition of S100A4 synthesis on osteoblast differentiation and in vitro mineralized nodule formation. Inhibition of S100A4 synthesis was achieved by an antisense approach in the mouse osteoblastic cell line MC3T3-E1. Cell clones that synthesized low levels of S100A4 (AS clones) produced markedly increased number of mineralized nodules at much earlier stages in comparison with controls as demonstrated by Alizarin red S and von Kossa staining. The expression of type I collagen (COLI) and osteopontin (OPN) increased in AS clones compared with controls. Bone sialoprotein (BSP) and osteocalcin (OCN), molecules associated with mineralization and markers for mature osteoblastic phenotype, were expressed in AS clones before their detection in controls. Because S100A4 was not localized in the nucleus of MC3T3-E1 cells and AS clones, it is unlikely that S100A4 directly regulates the expression of these genes. Moreover, the expression of Cbfal/Osf-2 and Osx, transcription factors necessary for the expression of osteoblast-associated genes, remained unchanged in AS clones, indicating that S100A4 may be downstream to these transcription factors. These findings indicate that S100A4 is a novel negative regulator of matrix mineralization likely by modulating the process of osteoblast differentiation.
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            Analysis of the presence of osteocalcin, S-100 protein, and proliferating cell nuclear antigen in cells of various types of osteosarcomas.

            Osteosarcomas are characterized by different histologic subtypes that are composed of heterogeneous tumor cells. Although the histological origin of the malignant cells is unknown, it has been speculated that osteoblasts lead to the malignant cells. In the current study, the osteosarcoma cells in 27 lesions were assessed by means of immunohistochemical staining for osteocalcin (OC), S-100 protein (S-100) and proliferating cell nuclear antigen (PCNA). PCNA labeling indices were the highest in osteoblastic and stromal areas, and significantly lower in chondroblastic areas (p < 0.01). Cells that were positive for both PCNA and OC were abundant in osteoblastic and stromal areas, while cells that were positive for both PCNA and S-100 were rarely observed. These results were almost similar for conventional, parosteal and periosteal osteosarcomas. In contrast, OC reactivity was poor in fibroblastic osteosarcoma, in osteosarcoma with giant cells, and in telangiectatic osteosarcoma. Pulmonary metastatic osteosarcoma lesions weakly expressed OC (p < 0.01), but showed high values for the PCNA labeling indices. In conclusion, immunohistochemical staining for OC, S-100, and PCNA are useful to analyze the proliferating cells in osteosarcomas. The main proliferating cells in most osteosarcomas are mature osteoblast-like cells. OC-negative tumor cells predominate in some of osteosarcoma subtypes, and these tumors therefore probably represent a distinct osteosarcoma variant. OC expression in pulmonary metastatic lesions may be suppressed.
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              Sonographic identification and measurement of the epiphyseal ossification centers as markers of fetal gestational age.

              This study was conducted to verify the predictive value of epiphyseal ossification center measurements in estimating gestational age. Women with singleton pregnancies of 30-40 weeks gestation (n = 377) were enrolled in this prospective study. The distal femoral, proximal tibial, and proximal humeral ossification centers were identified and measured. A nomogram of fetal bone development was created using the sum of the three diameters. Gestational age correlated well with the diameters of the distal femoral and the proximal tibial epiphyseal ossification centers but even better with the sum of the three ossification centers. Positive predictive values of the fetus having gestational age of at least 37 weeks when the sum of the three centers was 7, 11, and 13 mm were 82%, 94%, and 100%, respectively. A nomogram was created using the sum of the ossification centers for 30-40 weeks' gestational age. Ultrasonographic visualization of the epiphyses ossification centers may be a useful marker of fetal gestational age. Copyright 2005 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                + 48 052 5853705 , kizanat@cm.umk.pl
                Journal
                Surg Radiol Anat
                Surg Radiol Anat
                Surgical and Radiologic Anatomy
                Springer Paris (Paris )
                0930-1038
                1279-8517
                25 April 2017
                25 April 2017
                2017
                : 39
                : 11
                : 1235-1242
                Affiliations
                [1 ]Department of Normal Anatomy, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, The Nicolaus Copernicus University in Toruń, Łukasiewicza 1 Street, 85-821 Bydgoszcz, Poland
                [2 ]Department of Positron Emission Tomography and Molecular Imaging, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, The Nicolaus Copernicus University in Toruń, Łukasiewicza 1 Street, 85-821 Bydgoszcz, Poland
                Author information
                http://orcid.org/0000-0002-1249-6336
                Article
                1861
                10.1007/s00276-017-1861-8
                5644710
                28444434
                a7c0cf98-f085-40f2-863c-79aaea58fafb
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 8 January 2017
                : 20 April 2017
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag France SAS 2017

                Surgery
                femur,primary ossification center,size,growth dynamics,human fetus
                Surgery
                femur, primary ossification center, size, growth dynamics, human fetus

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