Ossification of the mandible: A regional composite model of intramembranous, parachondral, and endochondral mechanisms.

Authors

Mugurel Constantin Rusu, Adela Gabriela Stănescu, Răzvan Costin Tudose

Published in

Archives of oral biology. Volume 189. Pages 106664. Jun 17, 2026. Epub Jun 17, 2026.

Abstract

To catalogue the ossification mechanisms operating along the proximal-distal axis of the human mandible and integrate them into a unified regional framework.
Narrative review of embryological, molecular, transcriptomic, and clinical genetics evidence identified through structured searches of PubMed, Scopus, and Web of Science. The type of evidence (human, animal, in vitro, or combined) underpinning each major finding was tracked.
Five non-overlapping mechanisms operate across ten mandibular regions: (i) intramembranous ossification of the body, ramus, and coronoid process; (ii) parachondral ossification, defined as intramembranous bone formation in mesenchyme adjacent to Meckel's cartilage (MC) under MC-derived paracrine guidance (BMP5, BMP7, FGF7, SEMA3A from the intermediate MC) and used as the operative descriptor for mandibular body formation; (iii) endochondral ossification of primary cartilage at the symphysis and anterior MC midsegment, via chondrocyte-to-osteoblast transdifferentiation; (iv) endochondral ossification of secondary cartilage at the condylar and angular processes, with viable hypertrophic chondrocytes and chondroid bone; and (v) perichondral ossification at the MC surface. Transdifferentiation executes mechanism (iii) and is not a separate mode. Posterior MC degradation proceeds via autophagy, apoptosis, and chondroclastic resorption, with independent chondral centres near dental primordia contributing further. Treacher Collins syndrome, cleidocranial dysplasia, and Pierre Robin sequence reflect disruptions at different mechanistic levels.
The mandible is a composite structure employing multiple ossification modes in a region-specific manner; parachondral ossification most accurately characterises mandibular body formation. The framework carries translational implications for tissue engineering, distraction osteogenesis, and prenatal molecular rescue, evidenced only preclinically in a Treacher Collins mouse model.

PMID:
42320182
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

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