title: Retinoic acid modulates chondrogenesis in the developing mouse cranial base.
abstract: The retinoic acid (RA) signaling pathway is known to play important roles during craniofacial development and skeletogenesis. However, the specific mechanism involving RA in cranial base development has not yet been clearly described. This study investigated how RA modulates endochondral bone development of the cranial base by monitoring the RA receptor RARγ, BMP4, and markers of proliferation, programmed cell death, chondrogenesis, and osteogenesis. We first examined the dynamic morphological and molecular changes in the sphenooccipital synchondrosis-forming region in the mouse embryo cranial bases at E12-E16. In vitro organ cultures employing beads soaked in RA and retinoid-signaling inhibitor citral were compared. In the RA study, the sphenooccipital synchondrosis showed reduced cartilage matrix and lower BMP4 expression while hypertrophic chondrocytes were replaced with proliferating chondrocytes. Retardation of chondrocyte hypertrophy was exhibited in citral-treated specimens, while BMP4 expression was slightly increased and programmed cell death was induced within the sphenooccipital synchondrosis. Our results demonstrate that RA modulates chondrocytes to proliferate, differentiate, or undergo programmed cell death during endochondral bone formation in the developing cranial base.
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korean 21 Project, Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Korea.
authors.forename: Hyuk-Jae
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Jeong-Oh
authors.initials: JO
authors.lastname: Shin
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Cho
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D058574:Integrin-Binding Sialoprotein / Q000187:drug effects / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology; D009924:Organ Culture Techniques; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D015398:Signal Transduction; D019291:Skull Base / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D000097768:Retinoic Acid Receptor gamma
chemical_list: D000080462:Acyclic Monoterpenes; D055415:Bone Morphogenetic Protein 4; D058574:Integrin-Binding Sialoprotein; D019394:Ki-67 Antigen; D039821:Monoterpenes; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C007076:citral