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Histologic Comparison Of Physiologic And Pathologic Major Cranial Sutures: Does Cartilage Dysregulation Play A Role In Sagittal Craniosynostosis?
Anvith P. Reddy, MS1, Mera Fayek, BS
2, Reena Singh, MD
3, Christopher Bonfield, MD
4, Michael Golinko, MD
4, Wesley Thayer, MD/PhD
3, Galen Perdikis, MD
3, Matthew E. Pontell, MD
4.
1Vanderbilt University Medical School, Nashville, TN, USA,
2Vanderbilt University, Nashville, TN, USA,
3Vanderbilt University Medical Center, Nashville, TN, USA,
4Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, USA.
PURPOSE: The major cranial sutures are generally accepted to physiologically fuse via intramembranous ossification, yet confirmatory human data are limited. This study aims to establish a histologic atlas of physiologic major cranial sutures and compare these findings to those observed in premature suture fusion seen in craniosynostosis.
METHODS: Uninvolved sutures (sagittal n=2, coronal n=4, lambdoid n=2; 8-11 mo) and pathologic sutures (n=4, 3-4 mo) were sampled during open cranial vault remodeling procedures for patients with isolated, single-suture, non-syndromic craniosynostosis. Samples were sectioned and stained with H&E, Alizarin Red, Safranin O, Pentachrome, and Aggrecan immunofluorescence to assess ossification patterns and proteoglycan localization.
RESULTS: Physiologically open major sutures displayed osteogenic fronts separated by a dense mesenchymal zone with evidence of intramembranous ossification. Aggrecan, a chondrogenic acellular matrix marker that may be upregulated also in intramembranous ossification, was restricted to these fronts with distinct zonality. No histologic evidence of cartilage was seen in any open suture. In contrast, pathologic sagittal sutures demonstrated a hybrid ossification pattern with a complete loss of aggrecan zonality, evidenced by diffuse staining throughout the suture. Chondrocytes and overt cartilage were present during pathologic suture fusion.
CONCLUSIONS: This study provides the first high-resolution human histologic atlas of physiologic cranial sutures and establishes aggrecan zonality at the osteogenic fronts as a novel feature of physiologic development. In sagittal craniosynostosis, loss of zonality and emergence of chondrocytes reveal an endochondral ossification component not previously described in humans. These findings suggest that aberrant cartilage differentiation may contribute to nonsyndromic, single-suture sagittal craniosynostosis.
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