Optimal Timing for Intermittent Administration of Parathyroid Hormone (1-34) for Distraction Osteogenesis in Rabbits

BackgroundTo date, the usefulness of parathyroid hormone (PTH (1-34)) in distraction osteogenesis has been reported in several studies. We aimed to determine the optimal timing of PTH (1-34) administration in a rabbit distraction osteogenesis model.MethodsThe lower hind leg of a Japanese white rabbit was externally fixed, and tibial osteotomy was performed. One week after the osteotomy, bone lengthening was carried out at 0.375 mm/12 h for two weeks. After five weeks, the lower leg bone was collected. Bone mineral density (BMD), peripheral quantitative computed tomography (pQCT), micro-computed tomography (micro-CT), and mechanical tests were performed on the distracted callus. The rabbits were divided into three groups according to the timing of PTH administration: four weeks during the distraction and consolidation phases (group D+C), two weeks of the distraction phase (group D), and the first two weeks of the consolidation phase (group C). A control group (group N) was administered saline for four weeks during the distraction and consolidation phases. Furthermore, to obtain histological findings, lower leg bones were collected from each rabbit at two, three, and four weeks after osteotomy, and tissue sections of the distracted callus were examined histologically.ResultsThe BMD was highest in group C and was significantly higher than group D. In pQCT, the total cross-sectional area was significantly higher in groups D+C, D, and C than group N, and the cortical bone area was highest in group C and was significantly higher than group D. In micro-CT, group C had the highest bone mass and number of trabeculae. Regarding the mechanical test, group C had the highest callus failure strength, and this value was significantly higher compared to group N. There was no significant difference between groups D and N. The histological findings revealed that the distracted callus mainly consisted of endochondral ossification in the distraction phase. In the consolidation phase, the chondrocytes were almost absent, and intramembranous ossification was the main type of ossification.ConclusionWe found that the optimal timing of PTH (1-34) administration is during the consolidation phase, which is mainly characterized by intramembranous ossification.

Embryology of the head and neck

Development of the head is dominated by the changing shape of the brain and the formation of pharyngeal arches through which blood from the ventrally placed heart can pass to the dorsal aorta. The origin of the cell population within the head and neck is important as it predicts the behaviour and attributes of the cells and their progeny. The neural crest gives rise to an extensive mesenchymal population which contributes to the skull and enters and patterns the pharyngeal arches. The skull (neurocranium) forms around the developing brain and its emerging nerves. The base of the skull forms initially in cartilage (endochondral ossification) and the vault forms from neural crest mesenchyme (intramembranous ossification). The face and jaws (viscerocranium) form around the developing pharynx from a series of pharyngeal arches (numbered 1,2,3,4 and 6) which pass from the lateral sides of the pharynx to meet ventromedially.

The molecular complex of ciliary and golgin protein is critical for skull development

Intramembranous ossification, which consists of direct conversion of mesenchymal cells to osteoblasts, is a characteristic process in skull development. One critical role of these osteoblasts is to secrete collagen-containing bone matrix. However, it remains unclear how the dynamics of collagen trafficking is regulated during skull development. Here, we reveal the regulatory mechanisms of ciliary and golgin proteins required for intramembranous ossification. During normal skull formation, osteoblasts residing on the osteogenic front actively secreted collagen. Mass spectrometry and proteomic analysis determined endogenous binding between ciliary protein IFT20 and golgin protein GMAP210 in these osteoblasts. Like in Ift20 mutant mice, disruption of neural-crest specific GMAP210 in mice caused osteopenia-like phenotypes due to dysfunctional collagen trafficking. Mice lacking both IFT20 and GMAP210 displayed more severe skull defects compared to either IFT20 or GMAP210 mutants. These results demonstrate that the molecular complex of IFT20 and GMAP210 is essential for the intramembranous ossification during skull development.

Foramina parietalia permagna: descrizione di un caso clinico e revisione della letteratura

The purpose of the present work is to expose the defects of parietal bone ossification and to identify the criteria for differential diagnosis and brain changes related to the condition, with particular attention to the venous developmental anomalies and the pathological features associated. Foramina parietalia permagna (FPP) are caused by an insufficient intramembranous ossification around the parietal notch that is normally obliterated in the fifth month of normal foetal development. During the first few years of life as calvarial growth continues, cranium bifidum tends to resolve into two distinct, large parietal foramina. Most people with FPP have a positive family history as the condition is inherited in an autosomal dominant fashion with high, but incomplete penetrance. Mutations of either MSX2 or ALX4 genes are associated with enlarged parietal foramina. Meningeal cortical vascular malformation of the straight sinus and persistent falcine sinus have also been reported in the literature as possible associated anomalies.

Embryology of the Orbit

The orbit houses and protects the ocular globe and the supporting structures, and occupies a strategic position below the anterior skull base and adjacent to the paranasal sinuses. Its embryologic origins are inextricably intertwined with those of the central nervous system, skull base, and face. Although the orbit contains important contributions from four germ cell layers (surface ectoderm, neuroectoderm, neural crest, and mesoderm), a significant majority originate from the neural crest cells. The bones of the orbit, face, and anterior cranial vault are mostly neural crest in origin. The majority of the bones of the skull base are formed through endochondral ossification, whereas the cranial vault is formed through intramembranous ossification. Familiarity with the embryology and fetal development of the orbit can aid in understanding its anatomy, as well as many developmental anomalies and pathologic conditions that affect the orbit.

Dissecting human skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses

Human skeletal stem cells (SSCs) have been discovered in fetal and adult bones. However, the spatiotemporal ontogeny of human SSCs during embryogenesis has been elusive. Here we map the transcriptional landscape of human embryonic skeletogenesis at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, as well as the earliest osteo-chondrogenic progenitors. Importantly, embryonic SSCs (eSSCs) were found in the perichondrium of human long bones, which self-renew and generate osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSCs are marked by the adhesion molecule CADM1 and highly enrich FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional network were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.

Enhancement of BMP-2 and VEGF carried by mineralized collagen for mandibular bone regeneration

Repairing damage in the craniofacial skeleton is challenging. Craniofacial bones require intramembranous ossification to generate tissue-engineered bone grafts via angiogenesis and osteogenesis. Here, we designed a mineralized collagen delivery system for BMP-2 and vascular endothelial growth factor (VEGF) for implantation into animal models of mandibular defects. BMP-2/VEGF were mixed with mineralized collagen which was implanted into the rabbit mandibular. Animals were divided into (i) controls with no growth factors; (ii) BMP-2 alone; or (iii) BMP-2 and VEGF combined. CT and hisomputed tomography and histological staining were performed to assess bone repair. New bone formation was higher in BMP-2 and BMP-2-VEGF groups in which angiogenesis and osteogenesis were enhanced. This highlights the use of mineralized collagen with BMP-2/VEGF as an effective alternative for bone regeneration.