Differential Growth Factor Adsorption to Calvarial Osteoblast-Secreted Extracellular Matrices Instructs Osteoblastic Behavior

Craniosynostosis (CS), the premature ossification of cranial sutures, is attributed to increased osteogenic potential of resident osteoblasts, yet the contribution of the surrounding extracellular matrix (ECM) on osteogenic differentiation is unclear. The osteoblast-secreted ECM provides binding sites for cellular adhesion and regulates the transport and signaling of osteoinductive factors secreted by the underlying dura mater. The binding affinity of each osteoinductive factor for the ECM may amplify or mute its relative effect, thus contributing to the rate of suture fusion. The purpose of this paper was to examine the role of ECM composition derived from calvarial osteoblasts on protein binding and its resultant effect on cell phenotype. We hypothesized that potent osteoinductive proteins present during sutural fusion (e.g., bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-β1)) would exhibit distinct differences in binding when exposed to ECMs generated by human calvarial osteoblasts from unaffected control individuals (CI) or CS patients. Decellularized ECMs produced by osteoblasts from CI or CS patients were incubated in the presence of BMP-2 or TGF-β1, and the affinity of each protein was analyzed. The contribution of ECM composition to protein binding was interrogated by enzymatically modulating proteoglycan content within the ECM. BMP-2 had a similar binding affinity for each ECM, while TGF-β1 had a greater affinity for ECMs produced by osteoblasts from CI compared to CS patients. Enzymatic treatment of ECMs reduced protein binding. CS osteoblasts cultured on enzymatically-treated ECMs secreted by osteoblasts from CI patients in the presence of BMP-2 exhibited impaired osteogenic differentiation compared to cells on untreated ECMs. These data demonstrate the importance of protein binding to cell-secreted ECMs and confirm that protein-ECM interactions have an important role in directing osteoblastic differentiation of calvarial osteoblasts

Epiglottis reshaping using CO2 laser: A minimally invasive technique and its potent applications

Laryngomalacia (LRM), is the most common laryngeal abnormality of the newborn, caused by a long curled epiglottis, which prolapses posteriorly. Epiglottis prolapse during inspiration (acquired laryngomalacia) is an unusual cause of airway obstruction and a rare cause of obstructive sleep apnea syndrome (OSAS)

Nasal trumpet as a long-term remedy for obstructive sleep apnea syndrome in a child.

We present a case of successful long-term use of nasal trumpet for severe obstructive sleep apnea syndrome in a child with cerebral palsy and complex medical issues. Obstructive sleep apnea syndrome is frequently seen in pediatric patients with cerebral palsy due to their abnormal airway tone and pulmonary vulnerability. Identifying children with cerebral palsy who are at risk for obstructive sleep apnea syndrome is important because its treatment can improve quality of life and seizure control. Although first-line treatment for obstructive sleep apnea syndrome is adenotonsillectomy, children with cerebral palsy are more likely to have residual obstructive sleep apnea syndrome postoperatively. Other options such as positive airway pressure therapy and other upper airway surgeries may pose significant challenges and tolerance issues, as in our patient. As demonstrated in our report, the low rate of complications and ease of use make nasal trumpets a potential long-term treatment option for children with obstructive sleep apnea syndrome who fail or cannot comply with the traditional treatment options

Differential growth factor adsorption to calvarial osteoblast-secreted extracellular matrices instructs osteoblastic behavior.

Craniosynostosis (CS), the premature ossification of cranial sutures, is attributed to increased osteogenic potential of resident osteoblasts, yet the contribution of the surrounding extracellular matrix (ECM) on osteogenic differentiation is unclear. The osteoblast-secreted ECM provides binding sites for cellular adhesion and regulates the transport and signaling of osteoinductive factors secreted by the underlying dura mater. The binding affinity of each osteoinductive factor for the ECM may amplify or mute its relative effect, thus contributing to the rate of suture fusion. The purpose of this paper was to examine the role of ECM composition derived from calvarial osteoblasts on protein binding and its resultant effect on cell phenotype. We hypothesized that potent osteoinductive proteins present during sutural fusion (e.g., bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-β1)) would exhibit distinct differences in binding when exposed to ECMs generated by human calvarial osteoblasts from unaffected control individuals (CI) or CS patients. Decellularized ECMs produced by osteoblasts from CI or CS patients were incubated in the presence of BMP-2 or TGF-β1, and the affinity of each protein was analyzed. The contribution of ECM composition to protein binding was interrogated by enzymatically modulating proteoglycan content within the ECM. BMP-2 had a similar binding affinity for each ECM, while TGF-β1 had a greater affinity for ECMs produced by osteoblasts from CI compared to CS patients. Enzymatic treatment of ECMs reduced protein binding. CS osteoblasts cultured on enzymatically-treated ECMs secreted by osteoblasts from CI patients in the presence of BMP-2 exhibited impaired osteogenic differentiation compared to cells on untreated ECMs. These data demonstrate the importance of protein binding to cell-secreted ECMs and confirm that protein-ECM interactions have an important role in directing osteoblastic differentiation of calvarial osteoblasts

Unilateral and bilateral expression of a quantitative trait: asymmetry and symmetry in coronal craniosynostosis

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Alcian Blue stains of GAGs present in ECMs produced by CSObs (A) and CIObs (B) after heparanase (HS), chondroitinase ABC (CABC), both enzymes (BOTH) and without (CONTROL) enzyme treatment.

<p>Images taken at 100X magnification; scale bars represent 50 µm. C: Quantification of Alcian blue stain. *<i>p</i><0.05 vs. control, #<i>p</i><0.05 vs. CIObs ECM.</p