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Biomedical subjects

Jack C Yu

Publications and source records attributed to Jack C Yu.

5 recordsLinked to original sources

Brief synopsis of cranial sutures: optimization by adaptation.

This article reviews the form and function of cranial sutures across the temporal and spatial scales. The temporal scale spans 530 million years, from ostracoderms to contemporary humans. The spatial scale spans eight orders of magnitude, from the macroarchitectural level (the entire cranium), through the mesoarchitectural (the local/regional bone-suture-bone complex) and microarchitectural levels (tissues and cells), to the nanoarchitectural level (molecules within and outside the cells). A mechanomorphologic loop, or cycle, exists. The mechanical strain experienced by the sutures eventually alters the morphology of the sutures. In turn, these morphological changes affect the strain distribution within and around the sutures. At the microarchitectural level, the responses of bone and sutural cells to environmental perturbations depend on the content (what that perturbation is), the context (the other coexisting extrinsic and intrinsic factors), and the history of the perturbation (how often and for how long).

Animals↗

Tension-induced reduction in connexin 43 expression in cranial sutures is linked to transcriptional regulation by TBX2.

Cranial sutures produce bone at precisely the right rate and time to maintain homeostasis. Connexin 43 (CX43), a protein important for communication in bone, is downregulated during cell proliferation and is released from suppression or upregulated during differentiation. Our previous studies have shown that binding sites for the transcription regulatory protein TBX2 are located in the promoter sequence, upstream of the Cx43 gene. We have shown that TBX2 binding suppresses Cx43 expression. The current study uses transgenic mice in which the TBX2 promoter has been spliced upstream of the coding sequence for green fluorescent protein (GFP). This study shows upregulation of TBX2 after stretching. RNA from stretched and unstretched sutures was used for GeneChip and Western analysis. The results show an increase in Tbx2 and a decrease in Cx43 gene and protein expression with stretch. Our findings support a model of strain-regulated bone formation with feedback inhibition that maintains sutural patency during development.

Animals↗

Negative transcriptional regulation of connexin 43 by Tbx2 in rat immature coronal sutures and ROS 17/2.8 cells in culture.

BACKGROUND: Tbx2 is a member of the T-box family of transcriptional regulatory genes with an extensive but not yet fully understood role in embryonic development. This study explores the potential role of Tbx2 in calvarial morphogenesis. OBJECTIVES: To explore the hypothesis that Tbx2 has a negative regulatory effect on the expression of connexin 43 (Cx43), a protein necessary for cell-to-cell communication; document the presence of Tbx2 protein in the developing cranial sutures; and determine the spatial pattern of expression of this developmentally regulated transcription factor in calvariae. DESIGN: The osteoblast-like cell line ROS 17/2.8 was stably transfected with sense or antisense Tbx2. Immunohistochemistry and Western blotting was used to study Tbx2 and Cx43 expression in these cells and sections of embedded developing coronal sutures. RESULTS: The ROS 17/2.8 cells transfected with antisense Tbx2 showed a decrease in expression of Tbx2 protein and an increase in expression of endogenous Cx43. The reverse is seen with sense-transfected cells. Both of these proteins are expressed in rat developing coronal sutures. The pattern of Tbx2 expression in the developing was also reciprocal to the pattern of Cx43 expression. Tbx2 protein is concentrated in the center of the sutural blastema, an area devoid of Cx43 protein localization. Conversely, Tbx2 protein expression is low in the periphery of the sutures, in which there is high Cx43 protein expression. CONCLUSIONS: Taken together, these studies suggest that Tbx2 protein is a negative regulator of Cx43 expression at the transcriptional level in cranial sutures in vivo.

Animals↗

A fractal analysis of human cranial sutures.

OBJECTIVES: Many biological structures are products of repeated iteration functions. As such, they demonstrate characteristic, scale-invariant features. Fractal analysis of these features elucidates the mechanism of their formation. The objectives of this project were to determine whether human cranial sutures demonstrate self-similarity and measure their exponents of similarity (fractal dimensions). DESIGN: One hundred three documented human skulls from the Terry Collection of the Smithsonian Institution were used. Their sagittal sutures were digitized and the data converted to bitmap images for analysis using box-counting method of fractal software. RESULTS: The log-log plots of the number of boxes containing the sutural pattern, N(r), and the size of the boxes, r, were all linear, indicating that human sagittal sutures possess scale-invariant features and thus are fractals. The linear portion of these log-log plots has limits because of the finite resolution used for data acquisition. The mean box dimension, D(b), was 1.29289 +/- 0.078457 with a 95% confidence interval of 1.27634 to 1.30944. CONCLUSIONS: Human sagittal sutures are self-similar and have a fractal dimension of 1.29 by the box-counting method. The significance of these findings includes: sutural morphogenesis can be described as a repeated iteration function, and mathematical models can be constructed to produce self-similar curves with such D(b). This elucidates the mechanism of actual pattern formation. Whatever the mechanisms at the cellular and molecular levels, human sagittal suture follows the equation log N(r) = 1.29 log 1/r, where N(r) is the number of square boxes with sides r that are needed to contain the sutural pattern and r equals the length of the sides of the boxes.

Adolescent↗

Posttraumatic craniofacial reconstruction using combined resorbable and nonresorbable fixation systems.

The facial skeleton consists of high-stress-bearing buttresses and low-stress-bearing curved surfaces. The buttresses are like trusses made of beams, struts, and columns. They resist tensile, compressive, and shear loading. The thin, curved, planar surfaces provide for the support and partitioning of the soft tissue. The trusses are strong and one-dimensional whereas the planes are weak and two-dimensional. Ideally, strong one-dimensional fixation systems should be used for the former; weaker, two-dimensional systems should be used for the latter. The authors report their clinical experience of using such combined approaches to the treatment of facial fractures using rigid, titanium mini-plates and screws for the buttresses and polymeric resorbable meshes for the curved planes. For an 11-month period (August 2000 to June 2001), nine patients (7 males and 2 females) with a mean age of 33.7 years were treated in this fashion. The resorbable meshes were deployed for the reconstitution of the orbital walls and the anterior wall of the maxillary sinus. No enophthalmos, globe dystopia, or diplopia occurred during the short mean follow-up of 10 months (4-17 months). There were no infections or sterile abscess formations. This type of combined use of fixation systems appears to be safe and effective. More patients and more extensive follow-ups are obviously needed.

Absorbable Implants↗