Bone regeneration goal in sight

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VEGF: An essential mediator of both angiogenesis and endochondral ossification

During bone growth, development, and remodeling, angiogenesis as well as osteogenesis are closely associated processes, sharing some essential mediators. Vascular endothelial growth factor (VEGF) was initially recognized as the best-characterized endothelial-specific growth factor, which increased vascular permeability and angiogenesis, and it is now apparent that this cytokine regulates multiple biological functions in the endochondral ossification of mandibular condylar growth, as well as long bone formation. The complexity of VEGF biology is paralleled by the emerging complexity of interactions between VEGF ligands and their receptors. This narrative review summarizes the family of VEGF-related molecules, including 7 mammalian members, namely, VEGF, placenta growth factor (PLGF), and VEGF-B, -C, -D, -E, and -F. The biological functions of VEGF are mediated by at least 3 corresponding receptors: VEGFR-1/FIt-1, VEGFR-2/Flk-1, VEGFR-3/Flt-4 and 2 co-receptors of neuropilin (NRP) and heparan sulfate proteoglycans (HSPGs). Current findings on endochondral ossification are also discussed, with emphasis on VEGF-A action in osteoblasts, chondroblasts, and chondroclasts/osteoclasts and regulatory mechanisms involving oxygen tension, and some growth factors and hormones. Furthermore, the therapeutic implications of recombinant VEGF-A protein therapy and VEGF-A gene therapy are evaluated. Abbreviations used: VEGF, Vascular endothelial growth factor; PLGF, placenta growth factor; NRP, neuropilin; HSPGs, heparan sulfate proteoglycans; FGF, fibroblast growth factor; TGF, transforming growth factor; HGF, hepatocyte growth factor; TNF, tumor necrosis factor; ECM, extracellular matrix; RTKs, receptor tyrosine kinases; ERK, extracellular signal kinases; HIF, hypoxia-inducible factor.published_or_final_versio

Runx2 regulates endochondral ossification in condyle during mandibular advancement

Runx2 is a transcription factor prerequisite for chondrocyte maturation and osteoblast differentiation. We tested the hypothesis that Runx2 is responsible for signaling chondrocyte maturation and endochondral ossification in the condyle during mandibular advancement. Fifty 35-day-old Sprague-Dawley rats were fitted with functional appliances for 3, 7, 14, 21, and 30 days. Experimental animals with 50 matched controls were labeled with bromodeoxyuridine for evaluation of the invasion of chondroclasts and osteoblasts into condylar cartilage. Mandibular advancement elicited Runx2 expression in condylar cartilage, and subsequently led to an expansion of type X collagen domain in the hypertrophic layer. Stronger Runx2 mRNA signals in subchondral bone corresponded with the increase in the recruitment of osteoblasts and chondroclasts, which preceded the increase of new bone formation in the condyle. Thus, Runx2 mediates chondrocyte terminal maturation and endochondral ossification in the mandibular condyle in response to mandibular advancement.published_or_final_versio

Treatment of craniofacial syndromes by distraction osteogenesis: preliminary results

Congress Theme: Challenges to specialists in the 21st centurypublished_or_final_versio

PTHrP and Cbfal expression in condylar cartilage during pubertal growth

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Effect of DBM on the healing of intramembranous bone graft

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Quantitative evaluation of composite bone graft healing in rabbits

Abstract no. 328published_or_final_versio

Relationships between cranial base synchondroses and craniofacial development: a review

Abstract: Synchondrosis is defined as the development of a union between two bones by the formation of either hyaline cartilage or fibro-cartilage. This paper reviews the relationship between cranial base synchondroses and craniofacial development. The cranial base synchondroses are important growth centers of the craniofacial skeleton. Their abnormalities lead to numerous growth and developmental conditions in the craniofacial region. In dentofacial orthopedics, mechanical forces are commonly applied to cranial bones for growth modification to treat such conditions. Molecular biology and genetics provide tools to investigate the molecular mechanisms, genes and transcription factors responsible for synchondrosis and craniofacial development.published_or_final_versio

Indian hedgehog: A mechanotransduction mediator in condylar cartilage

Indian hedgehog (Ihh) is a critical mediator transducing mechanical signals to stimulate chondrocyte proliferation. To clarify the cellular signal transduction pathway that senses and converts mechanical signals into tissue growth in mandibular condyle, we evaluated Ihh expression and its relation to the kinetics of replicating mesenchymal cells in condylar cartilage during natural growth and mandibular advancement. Thirty-five-day-old Sprague-Dawley rats were fitted with functional appliances. Experimental animals with matched controls were doubly labeled with iododeoxyuridine and bromodeoxyuridine so that we could evaluate the cycles of the proliferative mesenchymal cells. Mandibular advancement triggered Ihh expression in condylar cartilage. A higher level of Ihh expression coincided with the increase of the replicating mesenchymal cells' population and the shortening of the turnover time. These findings suggested that Ihh acts as a mediator of mechanotransduction that converts mechanical signals resulting from anterior mandibular displacement to stimulate cellular proliferation in condylar cartilage.published_or_final_versio

Clinical effect of a topical herbal ointment on pain in temporomandibular disorders: A randomized placebo-controlled trial

Objectives: The aim of this study was to compare the effectiveness of using Ping On ointment and using petroleum jelly in the treatment of temporomandibular joint (TMJ) and masticatory muscle pain, in order to establish the true efficacy of Ping On ointment. Methods: In this randomized, double-blinded, placebo-controlled trial, 55 subjects with TMJ and/or masticatory pain (Group I patients according to the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD) received Ping On ointment for 4 weeks, or placebo for 4 weeks. Subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analogue scale and maximal comfortable mandibular opening, at baseline and again after 4 weeks of treatment. Results: Ping On ointment significantly reduced the symptoms of painful TMJs and/or masticatory muscles. Maximal comfortable mandibular opening also improved in the Ping On ointment group compared with the placebo, but was not clinically significant. Conclusions: This preliminary study suggests that topical application of Ping On ointment may be considered for further investigation as a potential first-line treatment modality, before prescribing analgesics, for the management of TMDs. It is topically applied, safe, reversible, and effective in managing TMDs and masticatory muscle pain. © 2009, Mary Ann Liebert, Inc.published_or_final_versio