Background: Bone morphogenetic proteins (BMPs) and their antagonists are involved in fracture healing. Antagonists regulate BMPs by blocking signal transduction or interfering with transcription factors at the nucleus. Objective: To examine targeting of BMP antagonists to manipulate osteogenesis. Methods: An overview of in vitro and in vivo evidence on effects of BMP antagonists on bone metabolism. Results/conclusion: There is in vitro evidence suggesting that overexpression of noggin and gremlin inhibits osteogenic differentiation, markedly decreases alkaline phosphatase (ALP) levels and impedes R-Smad (1/5/8) phosphorylation in murine cell lines. Knockdown of chordin results in a threefold increase in ALP activity in human mesenchymal stem cells. In vivo data shows that inhibition of noggin leads to increased bone regeneration in mice. Noggin and sclerostin can combine in a mutually inhibitory complex, neutralising their individual inhibitory effects. This allows BMP signalling to proceed to osteoinduction. We highlight the potential for clinical enhancement of bone formation through inhibition of BMP antagonists.
BACKGROUND: Lower lip reconstruction poses a particular challenge to the Maxillofacial Surgeon. As the major expressive component of the lower third of the face, preservation of both aesthetics and function is imperative. The most challenging reconstruction techniques involve major defects of >80% of the lower lip. There are many reconstructive techniques described using the remaining lip and local flaps to restore the lower lip dependent upon the size of the defect. Furthermore, no single technique has emerged as the ‘accepted standard’ and numerous modifications to existing surgical techniques continue to be documented in the literature. This case report describes the use of a novel one-stage bilateral labiomental fan flap for total lower lip reconstruction. METHOD: The authors applied their new reconstructive technique to an 81 year-old male with an extensive lower lip defect following excision of a fungating squamous cell carcinoma. Bilateral full thickness labiomental flaps were advanced and rotated to close the lower lip. A combination of mucosal advancement and free mucosal grafting was employed to reconstruct the lower vermillion. The advantages of our technique compared to the previously described techniques are as follows: Total preservation of upper lip anatomy (orbicualis oris and associated neurovascular structures) Preservation of lower lip anguli muscles and the use of well vascularized tissues thereby providing a recreating the oral sphincter, restoring oral competence and minimizing microstomia To our knowledge, this full thickness bilateral labiomental fan flap has not been described in the literature previously. RESULTS: The functional and aesthetic results following this flap reconstruction are acceptable. At 4 weeks post-operatively, our patient had good lower lip movement and sensation, near-normal mouth opening and function, total re-epithelization of the mucosal deficit and is extremely pleased with the aesthetic outcome. No further corrective surgery is deemed necessary. CONCLUSION: The authors conclude that this is a simple and easy to perform, one-stage technique that is associated with minimal morbidity and achieves acceptable outcomes for total lower lip reconstruction.
Mesenchymal stem cells (MSCs) are multipotent stromal cells characterized by their ability to differentiate into adipocytes, chondrocytes, osteocytes and a number of other lineages. Investigation into their use has increased in recent years as characterization of their immunomodulatory properties has developed, and their role in the pathophysiology of joint disease has been suggested.MSCs demonstrate immunosuppressive functionality by suppressing T- and B-cell responses following activation by cytokines such as IL-6 and IL-1α. They also can be induced to exert pro-inflammatory effects in the presence of acute inflammatory environment due to the actions of TNF-α and IFN-γ. In inflammatory joint diseases such as rheumatoid arthritis, MSCs in bone marrow migrate to joints by a TNF-α-dependent mechanism and may be in part responsible for the disease process. MSCs have also been demonstrated in increased numbers in periarticular tissues in osteoarthritis, which may reflect an attempt at joint regeneration.Clinical applications for MSCs have shown promise in a number of inflammatory and autoimmune disorders. Future work is likely to further reveal the immunosuppressive characteristics of MSCs, their role in the pathophysiology of joint diseases and provide the basis for new avenues for treatment.
Abstract The osteogenic molecular signals of the transforming growth factor‐β (TGF‐β) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs) and uniquely in primates the TGF‐β isoforms per se , pleiotropic members of the TGF‐β supergene family, induce de novo endochondral bone formation as a recapitulation of embryonic development. Naturally derived BMPs/OPs and gamma‐irradiated human recombinant osteogenic protein‐1 (hOP‐1) delivered by allogeneic and xenogeneic insoluble collagenous matrices initiate de novo bone induction in heterotopic and orthotopic sites of the primate Papio ursinus , culminating in complete calvarial regeneration by day 90 and maintaining the regenerated structures by day 365. The induction of bone by hOP‐1 in P. ursinus develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the TGF‐β superfamily that singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis. The temporal and spatial expressions of TGF‐β1 mRNA indicate a specific temporal transcriptional window during which expression of TGF‐β1 is mandatory for successful and optimal osteogenesis. Highly purified naturally derived bovine BMPs/OPs and hOP‐1 delivered by human collagenous bone matrices and porous hydroxyapatite, respectively, induce bone formation in mandibular defects of human patients. By using healthy body sites as bioreactors it is possible to recapitulate embryonic developments by inducing selected biomaterials combined with recombinant proteins to transform into custom‐made prefabricated bone grafts for human reconstruction. The osteogenic proteins of the TGF‐β superfamily, BMPs/OPs and TGF‐βs, the last endowed with the striking prerogative of inducing endochondral bone formation in primates only, are helping to engineer skeletal reconstruction in molecular terms.
INTRODUCTION: Orthognathic Surgery can have a substantial impact on a patient’s facial appearance, function, and quality of life. We evaluate 5 years’ of data on patients’ perception of their ‘Orthognathic Surgery’ experience using a standardised questionnaire. To our knowledge, we are the first Orthognathic Unit in the United Kingdom to provide long-term data on patient-centred outcomes following surgery. GOLD STANDARD: 90% satisfaction rate with ALL services provided during the Orthognathic Care Pathway. METHODS: In total, 103 patients who had undergone Orthognathic Surgery at Northwick Park Hospital between 2008 and 2013 were included in our 5-year audit. Patients were originally invited to complete a ‘paper’ patient satisfaction questionnaire, and in 2013 we introduced an online version of the questionnaire aiming to improve compliance. Our questionnaire addressed 53 parameters of care subdivided into 7 sections of the patient journey. RESULTS: Overall, the response rate averaged 70% per year. The majority of patients noted appearance as the most important motive for surgery. The psychological implications are unmistakable; nearly all patients report an improvement in facial appearance and self-esteem (95%). Significantly, there has been an increase in post-operative dietician support, management of pain and satisfaction with clinical staff. Post-operative surgical complications (e.g. sensory dysfunction) have also been explored. The overall satisfaction was very high (96%), the same percentage of patients ‘recommending’ the Unit. CONCLUSIONS: Our patient satisfaction survey has proved a useful tool for assessing aspects of clinical practice at Northwick Park Hospital. Evaluation of our data shows that great improvements continue to be made. We have introduced user-friendly ‘Pamphlets’ that is now part of our routine practice.
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