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Michael T Longaker - One of the best experts on this subject based on the ideXlab platform.

  • differential activation of canonical wnt signaling determines Cranial Sutures fate a novel mechanism for sagittal suture craniosynostosis
    Developmental Biology, 2010
    Co-Authors: Bjorn Behr, Michael T Longaker, Natalina Quarto
    Abstract:

    Premature closure of Cranial Sutures, which serve as growth centers for the skull vault, result in craniosynostosis. In the mouse posterior frontal (PF) suture closes by endochondral ossification, whereas sagittal (SAG) remain patent life time, although both are neural crest tissue derived. We therefore, investigated why Cranial Sutures of same tissue origin adopt a different fate. We demonstrated that closure of the PF suture is tightly regulated by canonical Wnt signaling, whereas patency of the SAG suture is achieved by constantly activated canonical Wnt signaling. Importantly, the fate of PF and SAG Sutures can be reversed by manipulating Wnt signaling. Continuous activation of canonical Wnt signaling in the PF suture inhibits endochondral ossification and therefore, suture closure, In contrast, inhibition of canonical Wnt signaling in the SAG suture, upon treatment with Wnt antagonists results in endochondral ossification and suture closure. Thus, inhibition of canonical Wnt signaling in the SAG suture phenocopies craniosynostosis. Moreover, mice haploinsufficient for Twist1, a target gene of canonical Wnt signaling which inhibits chondrogenesis, have sagittal craniosynostosis. We propose that regulation of canonical Wnt signaling is of crucial importance during the physiological patterning of PF and SAG Sutures. Importantly, dysregulation of this pathway may lead to craniosynostosis.

  • ex vivo model of Cranial suture morphogenesis and fate
    Cells Tissues Organs, 2009
    Co-Authors: Bethany J Slater, Kelly A. Lenton, Aaron W James, Michael T Longaker
    Abstract:

    Background/Aims: Craniosynostosis, the premature fusion of Cranial Sutures, is a common congenital defect. In vivo models for studying Cranial suture biology impose inherent restric

  • Cranial Sutures: a brief review.
    Plastic and Reconstructive Surgery, 2008
    Co-Authors: Bethany J Slater, Kelly A. Lenton, Matthew Kwan, Deepak M. Gupta, Michael T Longaker
    Abstract:

    Craniosynostosis, or the premature fusion of one or more Cranial Sutures, is a relatively common congenital defect that causes a number of morphologic and functional abnormalities. With advances in genetics and molecular biology, research of craniosynostosis has progressed from describing gross abnormalities to understanding the molecular interactions that underlie these Cranial deformities. Animal models have been extremely valuable in improving our comprehension of human craniofacial morphogenesis, primarily by human genetic linkage analysis and the development of knock-out animals. This article provides a brief review of perisutural tissue interactions, embryonic origins, signaling molecules and their receptors, and transcription factors in maintaining the delicate balance between proliferation and differentiation of cells within the suture complex that determines suture fate. Finally, this article discusses the potential implications for developing novel therapies for craniosynostosis.

  • Confocal laser scanning microscopic analysis of collagen scaffolding patterns in Cranial Sutures.
    The Journal of craniofacial surgery, 2008
    Co-Authors: Stephen M. Warren, Michael T Longaker, Benjamin Walder, Wojciech Dec, Kang Ting
    Abstract:

    Although recent studies indicate that regional dura mater influences the fate of the overlying Cranial suture, little is known about the assembly of extracellular matrix (ECM) molecules within the patent and fusing murine Cranial suture complexes. Confocal laser scanning microscopy was used to study ECM assembly within patent and fusing Cranial suture complexes. Coronal sections (20 μm thick) of patent sagittal (SAG) and fusing posterior frontal (PF) Sutures from postnatal 8-, 14-, and 18-day-old Sprague-Dawley rats were scanned in 0.5-μm increments, and images were collected consecutively to create a z-series for three-dimensional reconstruction. Spatial and temporal collagen arrangements were compared between SAG and PF Sutures by measuring interfiber distance, fiber thickness, and total collagen surface area at each time point. We demonstrate that on day 8 (before the onset of suture fusion), collagen bundles are randomly arranged in both the SAG and PF Sutures. By day 14 (midfusion period), there was a statistically significant reduction in total collagen surface area (80.5% versus 67.4%; P < 0.05) as the collagen bundles were organized into orthogonal lattices along the anterior and endoCranial margins of the PF suture. Furthermore, new bone matrix deposition was observed along the edges of these organized collagen bundles. In contrast, collagen within the SAG suture remained randomly arranged and unossified. By day 18 (late fusion period), the PF suture was completely fused except for the posterior-ectoCranial portion. This patent section of the PF suture contained a highly organized mineralizing orthogonal collagen lattice. The total collagen surface area in the day-18 PF suture continued to decline compared with the day-8 PF suture (80.5% versus 55.6%; P < 0.05). In the day-18 SAG suture, the collagen bundles remained randomly arranged, and the total surface area did not change. The same analysis was performed in a human pathologic fusing and patent suture. Similar results were observed. The total collagen surface area significantly decreased in the pathologic fusing human suture compared with the patent suture (92.8% versus 60.6%; P < 0.05). Moreover, the pathologically fusing suture contained a highly organized mineralizing orthogonal collagen lattice. This is the first analysis of collagen patterns in patent and fusing Cranial Sutures.

  • Expression and possible mechanisms of regulation of BMP3 in rat Cranial Sutures.
    Plastic and Reconstructive Surgery, 2005
    Co-Authors: Randall P. Nacamuli, Kelly A. Lenton, Kenton Fong, Hanjoon M. Song, Tony D. Fang, Ali Salim, Michael T Longaker
    Abstract:

    BACKGROUND: Clinical genetics data and investigative studies have contributed greatly to our understanding of the role of numerous genes in craniosynostosis. Recent studies have introduced antagonists of osteogenesis as potential key regulators of suture fusion and patency. The authors investigated the expression pattern of the bone morphogenetic protein antagonist BMP3 in rat Cranial Sutures and the factors regulating its expression in vitro. METHODS: Microarray analysis was performed on rat posterior frontal and sagittal Cranial Sutures at 5, 10, 15, 20, and 30 days of life (n = 30 per group). Gene expression was confirmed using quantitative real-time reverse transcriptase polymerase chain reaction. Regulation of BMP3 expression was determined using primary rat calvarial osteoblasts stimulated with recombinant human fibroblast growth factor 2 or recombinant human transforming growth factor beta1, or cultured with primary rat nonsuture dura mater. Gene expression was quantified with quantitative real-time reverse transcriptase polymerase chain reaction. RESULTS: BMP3 expression in the posterior frontal suture decreased over the time course analyzed, whereas it increased in the sagittal suture. Notably, BMP3 expression was higher in the patent sagittal suture during the window of posterior frontal suture fusion. Stimulation of osteoblasts with recombinant human fibroblast growth factor 2 led to a rapid and sustained suppression of BMP3 expression (85 percent, p < 0.01) when compared with controls. Co-culture with dural cells decreased BMP3 mRNA by 50 percent compared with controls (p < 0.01). CONCLUSIONS: BMP3 is expressed in rat Cranial Sutures in a temporal pattern suggesting involvement in Cranial suture patency and fusion. Furthermore, BMP3 is regulated in calvarial osteoblasts by recombinant human fibroblast growth factor 2 and by paracrine signaling from dura mater. These data add to our knowledge of the role of osteogenic antagonists in Cranial suture biology.

Felix Beckmann - One of the best experts on this subject based on the ideXlab platform.

  • synchrotron microcomputed tomography studies of normal and pathological Cranial Sutures further insight
    Journal of Neurosurgery, 2010
    Co-Authors: Jan Regelsberger, Tobias Schmidt, Björn Busse, Julia Herzen, Michael Tsokos, Michael Amling, Felix Beckmann
    Abstract:

    Object Both CT and high-frequency ultrasound have been shown to be reliable diagnostic tools used to differentiate normal Cranial Sutures from suture synostosis. In nonsynostotic plagiocephaly, overlapping of the bony plates and the so-called “sticky suture” is still controversial and is believed to represent a pathological fusion process. Synchrotron–microcomputed tomography (SRmCT) studies were undertaken to determine whether positional head deformities can be assumed to be true suture pathologies. Methods Morphological features and growth development of 6 normal Cranial Sutures between the ages of 3 and 12 months were analyzed histologically. Additionally 6 pathological Sutures, including sagittal synostosis and nonsynostotic plagiocephaly (NSP), were compared with the group of normal Sutures by histological and SRmCT studies. Synchrotron-microcomputed tomography is a special synchrotron radiation source with a high photon flux providing a monochromatic x-ray beam with a very high spatial resolution. M...

  • Synchrotron–microcomputed tomography studies of normal and pathological Cranial Sutures: further insight
    Journal of neurosurgery. Pediatrics, 2010
    Co-Authors: Jan Regelsberger, Tobias Schmidt, Björn Busse, Julia Herzen, Michael Tsokos, Michael Amling, Felix Beckmann
    Abstract:

    Object Both CT and high-frequency ultrasound have been shown to be reliable diagnostic tools used to differentiate normal Cranial Sutures from suture synostosis. In nonsynostotic plagiocephaly, overlapping of the bony plates and the so-called “sticky suture” is still controversial and is believed to represent a pathological fusion process. Synchrotron–microcomputed tomography (SRmCT) studies were undertaken to determine whether positional head deformities can be assumed to be true suture pathologies. Methods Morphological features and growth development of 6 normal Cranial Sutures between the ages of 3 and 12 months were analyzed histologically. Additionally 6 pathological Sutures, including sagittal synostosis and nonsynostotic plagiocephaly (NSP), were compared with the group of normal Sutures by histological and SRmCT studies. Synchrotron-microcomputed tomography is a special synchrotron radiation source with a high photon flux providing a monochromatic x-ray beam with a very high spatial resolution. M...

Babak J Mehrara - One of the best experts on this subject based on the ideXlab platform.

  • regional differentiation of rat Cranial suture derived dural cells is dependent on association with fusing and patent Cranial Sutures
    Plastic and Reconstructive Surgery, 1999
    Co-Authors: Babak J Mehrara, Joshua A Greenwald, Gyu S Chin, Matthew E Dudziak, Julide Sagrioglu, Douglas S Steinbrech, Pierre B Saadeh, George K Gittes, Michael T Longaker
    Abstract:

    A significant body of literature supports a role for the dura mater underlying Cranial Sutures in the regulation of sutural fate. These studies have implicated regional differentiation of the dura mater based on association with fusing and patent rat Cranial Sutures. The purpose of these experiments

  • Regional differentiation of rat Cranial suture-derived dural cells is dependent on association with fusing and patent Cranial Sutures.
    Plastic and reconstructive surgery, 1999
    Co-Authors: Babak J Mehrara, Joshua A Greenwald, Gyu S Chin, Matthew E Dudziak, Julide Sagrioglu, Douglas S Steinbrech, Pierre B Saadeh, George K Gittes, Michael T Longaker
    Abstract:

    A significant body of literature supports a role for the dura mater underlying Cranial Sutures in the regulation of sutural fate. These studies have implicated regional differentiation of the dura mater based on association with fusing and patent rat Cranial Sutures. The purpose of these experiments was to isolate and characterize dural cells associated with fusing (posterior frontal) and patent (sagittal) rat Cranial Sutures. Six-day-old rats were killed, and the dura mater underlying the posterior frontal and sagittal Sutures was harvested. Dural cells were briefly trypsinized and allowed to reach confluence. Two litters (10 animals per litter) were used for each set of experiments. Cells were harvested after the first and fifth passages for analysis of vimentin and desmoplakin expression (characteristic of human meningeal cells), cellular proliferation, density at confluence (a measure of cellular contact inhibition), and alkaline phosphatase production. In addition, bone nodule formation and collagen I production were analyzed in first passage cells. The results indicate that suture-derived dural cells can be established and that these cells coexpress vimentin and desmoplakin. In addition, it is demonstrated that first-passage sagittal suture-derived dural cells proliferate significantly faster and have decreased cellular contact inhibition than posterior frontal suture-derived cells (p < 0.01). Finally, it is shown that suture-derived dural cells have osteoblast-like properties, including alkaline phosphatase production, collagen I expression, and bone nodule formation in vitro. The possible mechanisms by which regional differentiation of suture-derived dural cells occur are discussed.

  • immunolocalization of basic fibroblast growth factor and fibroblast growth factor receptor 1 and receptor 2 in rat Cranial Sutures
    Plastic and Reconstructive Surgery, 1998
    Co-Authors: Babak J Mehrara, George K Gittes, Richard J Mackool, Joseph G Mccarthy, Michael T Longaker
    Abstract:

    Craniosynostosis is a common disorder with an unknown etiology. Recent genetic mapping studies have demonstrated a strong linkage between several familial craniosynostotic syndromes and mutations in fibroblast growth factor receptor 1 (FGF-R1) and 2 (FGF-R2). The purpose of this experiment was to investigate by immunohistochemistry the protein production of these receptors as well as of their most prevalent ligand, basic fibroblast growth factor (bFGF), before, during, and after sutural fusion in rat Cranial Sutures. The posterior frontal (normally fuses between postnatal days 12 and 22) and sagittal (remains patent) Sutures of embryonic day 20 and neonatal days 6, 12, 17, 22, and 62 (n = 3 per group) were harvested, fixed, and decalcified. Five-micrometer sections were stained with polyclonal antibodies against bFGF, FGF-R1, and FGF-R2, and patterns of immunohistochemical staining were assessed by independent reviewers. Our results indicate that increased bFGF production correlates temporally with suture fusion, with increased staining of the dura underneath the fusing suture prior to fusion followed by increased staining within osteoblasts and sutural cells during fusion. FGF-R1 and, to a lesser extent, FGF-R2 immunostaining revealed a different pattern of localization with increased immunostaining within the patent sagittal suture at these time points. These results implicate bFGF in the regulation of sutural fusion and may imply autoregulatory mechanisms in fibroblast growth factor receptor expression. (Plast. Reconstr. Surg. 102: 1805, 1998.)

Bruno Della Pietra - One of the best experts on this subject based on the ideXlab platform.

  • Undetected traumatic diastasis of Cranial Sutures: a case of child abuse.
    Forensic Science International, 2019
    Co-Authors: Carlo Pietro Campobasso, Francesco De Micco, Valentina Bugelli, Antonio Cavezza, William C. Rodriguez, Bruno Della Pietra
    Abstract:

    Traumatic diastasis of Cranial Sutures is a type of bone fracture more common in children than in adults, but little attention has been paid to this skull damage. Differentiation between inflicted and accidental traumatic head injury is still a challenge in forensic pathology, particularly in pediatric population. In fact, diastasis of Cranial Sutures may occur with or without other skull fractures and may be the only evidence of an abusive head trauma (AHT). This is a case study dealing with undetected traumatic diastasis of Cranial Sutures in child abuse. The skeletonized juvenile remains were found inside a suitcase. A diastasis of the coronal and sagittal Sutures was the only finding recorded at the autopsy with no other relevant bone defects. The diastasis was originally attributed by the medical examiner to a physiological unfused stage of the calvarial bones. Therefore, the cause of death was undetermined. Twelve years later an anthropological revision of the cold case showed that diastasis of the coronal and sagittal Sutures was assessed as the evidence of an AHT. Analysis of skull fractures in child abuse can be challenging as normal skull suture variants mimicking intentional injury are reported. Diastasis of the Cranial Sutures can be also a post-mortem effect of burning or freezing. Therefore, a differential diagnosis between natural, accidental or inflicted skull defects is mandatory in death investigation. A multidisciplinary approach in such circumstances is strongly recommended in order to reduce the risk of misdiagnosis.

Carlo Pietro Campobasso - One of the best experts on this subject based on the ideXlab platform.

  • Undetected traumatic diastasis of Cranial Sutures: a case of child abuse.
    Forensic Science International, 2019
    Co-Authors: Carlo Pietro Campobasso, Francesco De Micco, Valentina Bugelli, Antonio Cavezza, William C. Rodriguez, Bruno Della Pietra
    Abstract:

    Traumatic diastasis of Cranial Sutures is a type of bone fracture more common in children than in adults, but little attention has been paid to this skull damage. Differentiation between inflicted and accidental traumatic head injury is still a challenge in forensic pathology, particularly in pediatric population. In fact, diastasis of Cranial Sutures may occur with or without other skull fractures and may be the only evidence of an abusive head trauma (AHT). This is a case study dealing with undetected traumatic diastasis of Cranial Sutures in child abuse. The skeletonized juvenile remains were found inside a suitcase. A diastasis of the coronal and sagittal Sutures was the only finding recorded at the autopsy with no other relevant bone defects. The diastasis was originally attributed by the medical examiner to a physiological unfused stage of the calvarial bones. Therefore, the cause of death was undetermined. Twelve years later an anthropological revision of the cold case showed that diastasis of the coronal and sagittal Sutures was assessed as the evidence of an AHT. Analysis of skull fractures in child abuse can be challenging as normal skull suture variants mimicking intentional injury are reported. Diastasis of the Cranial Sutures can be also a post-mortem effect of burning or freezing. Therefore, a differential diagnosis between natural, accidental or inflicted skull defects is mandatory in death investigation. A multidisciplinary approach in such circumstances is strongly recommended in order to reduce the risk of misdiagnosis.

  • Undetected Traumatic Diastasis in a case of Child Abuse
    2019
    Co-Authors: Carlo Pietro Campobasso, De Micco F, Cavezza A, Wc Rodriguez, Della Pietra B
    Abstract:

    Traumatic diastasis of Cranial Sutures is a type of bone fracture more common in children than in adults, but little attention has been paid to this skull damage. Differentiation between inflicted and accidental traumatic head injury is still a challenge in forensic pathology, particularly in pediatric population. In fact, diastasis of Cranial Sutures may occur with or without other skull fractures and may be the only evidence of an abusive head trauma (AHT). This is a case study dealing with undetected traumatic diastasis of Cranial Sutures in child abuse. The skeletonized juvenile remains were found inside a suitcase. A diastasis of the coronal and sagittal Sutures was the only finding recorded at the autopsy with no other relevant bone defects. The diastasis was originally attributed by the medical examiner to a physiological unfused stage of the calvarial bones. Therefore, the cause of death was undetermined. Twelve years later an anthropological revision of the cold case showed that diastasis of the coronal and sagittal Sutures was assessed as the evidence of an AHT. Analysis of skull fractures in child abuse can be challenging as normal skull suture variants mimicking intentional injury are reported. Diastasis of the Cranial Sutures can be also a post-mortem effect of burning or freezing. Therefore, a differential diagnosis between natural, accidental or inflicted skull defects is mandatory in death investigation. A multidisciplinary approach in such circumstances is strongly recommended in order to reduce the risk of misdiagnosis