Osteogenic and Angiogenic Profiles of Mandibular Bone-Forming Cells

Abstract

The mandible is a tooth-bearing structure involving one of the most prominent bones of the facial region. Mesenchymal cell condensation is the first morphological sign of osteogenesis, and several studies have focused on this stage also in the mandible. Little information is available about the early post-condensation period, during which avascular soft condensation turns into vascularized bone, and all three major bone cell types, osteoblasts, osteocytes, and osteoclasts, differentiate. In the mouse first lower molar region, the post-condensation period corresponds to the prenatal days 13–15. If during this critical period, when osteogenesis reaches the point of major bone cell differentiation, vascularization already has to play a critical role, one should be able to show molecular changes which support both types of cellular events. The aim of the present report was to follow in organ context the expression of major osteogenic and angiogenic markers and identify those that are up- or downregulated during this period. To this end, PCR Array was applied covering molecules involved in osteoblastic cell proliferation, commitment or differentiation, extracellular matrix (ECM) deposition, mineralisation, osteocyte maturation, angiogenesis, osteoclastic differentiation, and initial bone remodeling. From 161 analyzed osteogenic and angiogenic factors, the expression of 37 was altered when comparing the condensation stage with the bone stage. The results presented here provide a molecular survey of the early post-condensation stage of mandibular/alveolar bone development which has not yet been investigated in vivo .

Formation and Developmental Specification of the Odontogenic and Osteogenic Mesenchymes

“…Within 2 days, from ED13 to ED15, when cell differentiation occurs, the osteogenic condensation turns into a vascularized bone containing bone specific cells: (e.g., Alfaqeeh et al, 2013 ; Vesela et al, 2019 ). From ED15, the bony crypt around the dental primordia starts to be remodeled, mostly by bone resorption ( Radlanski et al, 2015 ).…”

“…Very quickly, this mesenchyme shows further peculiarity. Immunostainings for VEGFR2, CD31, CD34 showed that the interstitial mesenchyme is vascularized at ED14, slightly before the dental mesenchyme and before the forming bone itself ( Nait Lechguer et al, 2008 ; Keller et al, 2012 ; Vesela et al, 2019 ).…”

“…Furthermore, during tooth development, vascularization is anticipated in the interstitial mesenchyme, and blood vessels do not enter the condensed mesenchyme before the cap stage tooth germ as stated above. Similarly, blood vessels do not enter the osteogenic condensation before ED14 ( Vesela et al, 2019 ).…”

“…Besides bone cells stricto sensu , blood vessels penetrate the osteogenous condensation at ED14, and the bone structure is vascularized by ED15 ( Vesela et al, 2019 ). As reported in the case of the dental papilla, blood vessels play a major role in bone homeostasis, in regulating the osteogenic microenvironment, bringing minerals, growth factors, and osteogenic progenitor cells (e.g., Grosso et al, 2017 ).…”

Specification of Sprouty2 functions in osteogenesis in in vivo context

“…Morphological/histological criteria were analyzed after trichrome staining (hematoxylin, alcian blue, sirius red) and TRAP staining, as previously described. 11 Immunohistochemical detection was performed to show the expression of markers and better specify cell heterogeneity within the developing bone. Antigen retrieval was carried out in citrate buffer (pH = 6.0) for 5 min at 98°C for all markers.…”