Bone up: craniomandibular development and hard-tissue biomineralization in neonate mice

Abstract

The presence of regional variation in the osteogenic abilities of cranial bones underscores the fact that the mechanobiology of the mammalian skull is more complex than previously recognized. However, the relationship between patterns of cranial bone formation and biomineralization remains incompletely understood. In four strains of mice, micro-computed tomography was used to measure tissue mineral density during perinatal development in three skull regions (calvarium, basicranium, mandible) noted for variation in loading environment, embryological origin, and ossification mode. Biomineralization levels increased during perinatal ontogeny in the mandible and calvarium, but did not increase in the basicranium. Tissue mineral density levels also varied intracranially, with the mandible being greatest, the basicranium intermediate, and the calvarium lowest. Perinatal increases in, and elevated levels of, mandibular biomineralization appear related to the impending postweaning need to resist elevated masticatory stresses. Similarly, perinatal increases in calvarial biomineralization may be linked to ongoing brain expansion, which is known to stimulate sutural bone formation in this region. The lack of perinatal increase in basicranial biomineralization could be a result of earlier developmental maturity in the cranial base relative to other skull regions due to its role in supporting the brain’s mass throughout ontogeny. These results suggest that biomineralization levels and age-related trajectories throughout the skull are influenced by the functional environment and ontogenetic processes affecting each region, e.g., onset of masticatory loads in the mandible, whereas variation in embryology and ossification mode may only have secondary effects on patterns of biomineralization. Knowledge of perinatal variation in tissue mineral density, and of normal cranial bone formation early in development, may benefit clinical therapies aiming to correct developmental defects and traumatic injuries in the skull, and more generally characterize loading environments and skeletal adaptations in mammals by highlighting the need for multi-level analyses for evaluating functional performance of cranial bone.

Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency

“…A possible reason for the failure of metformin to rescue cranial width is that the age-related trajectories throughout the craniofacial bone are affected by the functional specific chemical or physical niches, as well as ontogenetic processes influencing each region. 27 However, our understanding of cranial bone formation at different regions during early development still needs to be further improved. 28 Our results showed that metformin also promoted bone formation of OC-Cre; Pck2 f/f mice femurs at P0 and P5, as assessed by the HE staining (Fig.…”

Synthetic materials in craniofacial regenerative medicine: A comprehensive overview

“…Some examples are electrospun nanofibrous scaffolds and rapid prototyping technologies such as SLA, DLP, SLS, and 3DP ( Yuan et al, 2017 ; Udomluck et al, 2020 ). Bone matrix production shows differences in endochondral and intramembranous grafts suggesting a site-specific bone formation pattern based on the form of cranial bone ossification ( Thompson et al, 2017 ). Osteoconduction and osteoinduction properties of demineralized bone matrix (DBM), especially from cortical bone have made it a proper osteoinductive matrix ( Ansari, 2019 ).…”

Morphological association between muscle attachments and ossification sites in the late cartilaginous skull of tuatara embryos

“…When embryonic muscles contract in fetal movements, they can produce a mechanical load on cartilages and bones. It has been argued that the mechanical load induced by muscles might affect chondrification and ossification in embryonic development (Balanta‐Melo et al, 2019; Conith et al, 2019; Moore, 2010; Sella‐Tunis et al, 2018; Spassov et al, 2017; K. D. Thompson et al, 2017; Weijs & Hillen, 1986). With the invention and application of neuromuscular blocking agents, which cause paralysis of vertebrate embryos, researchers became capable of investigating muscle–bone interaction (Drachman & Coulombre, 1962).…”

“…When embryonic muscles contract in fetal movements, they can produce a mechanical load on cartilages and bones. It has been argued that the mechanical load induced by muscles might affect chondrification and ossification in embryonic development (Balanta-Melo et al, 2019;Conith et al, 2019;Moore, 2010;Sella-Tunis et al, 2018;Spassov et al, 2017;K. D. Thompson et al, 2017;Weijs & Hillen, 1986).…”