Epithelium-poor Odontogenic Fibroma with an Unusual Progress

Odontogenic fibroma (OF) is a relatively rare benign tumor derived from odontogenic ectodermal mesenchymal tissue. It is divided into central (COF) or peripheral OF (POF) based on the affected area. Regarding its pathological features, OF can also be classified as epithelium-rich (WHO type) or epithelium-poor (simple type), depending on the amount of odontogenic epithelium in the tumor. There is limited information available about the latter type because of its low incidence. We report case of simple type COF apparently like POF. A 52- year-old Japanese male was suffering from tenderness at the right posterior maxilla during occlusion with his removable partial denture. The lesion was diagnosed as a simple type OF arising at the edentulous region around the right molar site of the maxilla. A tumor resection was performed, and there was no evidence of recurrence at his 18-month follow-up examination. In addition, we provide a review of the literature with the most up-to-date information about this lesion so that it can be diagnosed correctly

Roles of heterotypic CCN2/CTGF-CCN3/NOV and homotypic CCN2-CCN2 interactions in expression of the differentiated phenotype of chondrocytes

To identify proteins that regulate CCN2 activity, we carried out GAL4-based yeast two-hybrid screening with a cDNA library derived from a chondrocytic cell line, HCS-2/8. CCN2/CTGF and CCN3/NOV polypeptides were picked up as CCN2-binding proteins, and CCN2CCN2 and CCN2CCN3 binding domains were identified. Direct binding between CCN2 and CCN3 was confirmed by coimmunoprecipitation in vitro and in vivo and surface plasmon resonance, and the calculated dissociation constants (Kd) were 1.17 x 10-9 m for CCN2 and CCN2, and 1.95 x 10-9 m for CCN2 and CCN3. Ectopically overexpressed green fluorescent proteinCCN2 and HaloCCN3 in COS7 cells colocalized, as determined by direct fluorescence analysis. We present evidence that CCN2CCN3 interactions modulated CCN2 activity such as enhancement of ACAN and col2a1 expression. Curiously, CCN2 enhanced, whereas CCN3 inhibited, the expression of aggrecan and col2a1 mRNA in HCS-2/8 cells, and combined treatment with CCN2 and CCN3 abolished the inhibitory effect of CCN3. These effects were neutralized with an antibody against the von Willebrand factor type C domain of CCN2 (11H3). This antibody diminished the binding between CCN2 and CCN2, but enhanced that between CCN3 and CCN2. Our results suggest that CCN2 could form homotypic and heterotypic dimers with CCN2 and CCN3, respectively. Strengthening the binding between CCN2 and CCN3 with the 11H3 antibody had an enhancing effect on aggrecan expression in chondrocytes, suggesting that CCN2 had an antagonizing effect by binding to CCN3

CCN3 and bone marrow cells

CCN3 expression was observed in a broad variety of tissues from the early stage of development. However, a kind of loss of function in mice (CCN3 del VWC domain -/-) demonstrated mild abnormality, which indicates that CCN3 may not be critical for the normal embryogenesis as a single gene. The importance of CCN3 in bone marrow environment becomes to be recognized by the studies of hematopoietic stem cells and Chronic Myeloid Leukemia cells. CCN3 expression in bone marrow has been denied by several investigations, but we found CCN3 positive stromal and hematopoietic cells at bone extremities with a new antibody although they are a very few populations. We investigated the expression pattern of CCN3 in the cultured bone marrow derived mesenchymal stem cells and found its preference for osteogenic differentiation. From the analyses of in vitro experiment using an osteogenic mesenchymal stem cell line, Kusa-A1, we found that CCN3 downregulates osteogenesis by two different pathways; suppression of BMP and stimulation of Notch. Secreted CCN3 from Kusa cells inhibited the differentiation of osteoblasts in separate culture, which indicates the paracrine manner of CCN3 activity. CCN3 may also affect the extracellular environment of the niche for hematopoietic stem cells

Short lingual osteotomy without fixation: a new strategy for mandibular osteotomy known as “physiological positioning”

We describe the strategy of physiological positioning, which we regard as a new alternative treatment to conventional orthognathic operations, and treated 18 patients with skeletal mandibular prognathism using it. The positions of SNB, FMA, and Me were measured postoperatively to assess skeletal stability, changes in the angle and perpendicular length of the upper and lower central incisors were measured to assess dental stability, and we confirmed that both skeletal and dental stability were excellent. The width to which the jaw could be opened recovered early, and we saw only one case of disorder of the temporomandibular joint. Short lingual osteotomy with physiological positioning is an effective new approach to the treatment of deformities of the mandible

Proteins on the catwalk: modelling the structural domains of the CCN family of proteins

The CCN family of proteins (CCN1, CCN2, CCN3, CCN4, CCN5 and CCN6) are multifunctional mosaic proteins that play keys roles in crucial areas of physiology such as angiogenesis, skeletal development tumourigenesis, cell proliferation, adhesion and survival. This expansive repertoire of functions comes through a modular structure of 4 discrete domains that act both independently and in concert. How these interactions with ligands and with neighbouring domains lead to the biological effects is still to be explored but the molecular structure of the domains is likely to play an important role in this. In this review we have highlighted some of the key features of the individual domains of CCN family of proteins based on their biological effects using a homology modelling approach

CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis

The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity. These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease. In this review, we focus on CCN3, a founding member of this family, and its role in regulating cells within the bone microenvironment. CCN3 impairs normal osteoblast differentiation through multiple mechanisms, which include the neutralization of pro-osteoblastogenic stimuli such as BMP and Wnt family signals or the activation of pathways that suppress osteoblastogenesis, such as Notch. In contrast, CCN3 is known to promote chondrocyte differentiation. Given these functions, it is not surprising that CCN3 has been implicated in the progression of primary bone cancers such as osteosarcoma, Ewing’s sarcoma and chondrosarcoma. More recently, emerging evidence suggests that CCN3 may also influence the ability of metastatic cancers to colonize and grow in bone

Regulation of osteoblast differentiation mediated by BMP, Notch, and CCN3/NOV

Osteoblasts originate from common progenitors, which are capable of differentiating into other mesenchymal cell lineages such as chondrocytes, myoblasts and adipocytes. Various hormones and cytokines regulate osteoblast differentiation of mesenchymal progenitors to osteoblasts. Among these, bone morphogenetic proteins (BMPs) are the most potent inducers and stimulators of osteoblast differentiation: BMPs not only stimulate osteoprogenitors to differentiate into mature osteoblasts but also induce non-osteogenic cells to differentiate into osteoblast lineage cells. BMPs are important local factors that regulate Runx2, which is an essential transcription factor for osteoblast differentiation. The Notch signaling pathway is involved in a variety of cellular function, including cell proliferation, differentiation and apoptosis. Notch signaling has a dual effect on osteoblast differentiation. In terms of stimulation, functional Notch signaling is essential not only for BMP-2-induced osteoblast differentiation but also for BMP signaling itself. CCN3/NOV, a member of the CCN family of proteins, exerts inhibitory effects on BMP-2-induced osteoblast differentiation via its involvement in the BMP and Notch signaling pathways. Thus, osteoblast differentiation is critically regulated by the intimate interaction of various signaling molecules including BMP, Notch and CCN3/NOV