Long-term haplodeficency of DSPP causes temporomandibular joint osteoarthritis in mice.

BACKGROUND: Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. MATERIALS AND METHODS: To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. RESULTS: Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. CONCLUSIONS: Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.

Mandibular Reconstruction Using Free Fibular Flap Graft Following Excision of Calcifying Epithelial Odontogenic Tumor.

ABSTRACT: The calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic tumor, which usually presents with distension of affected tissues. Radiologically, the lesions are often associated with an unerupted tooth and may have spot calcification shadows. The authors report a case of a CEOT in a 48-year-old male involving the right mandibular jaw bone and mentum soft tissues. The authors performed hemimandibulectomy and enucleation followed by reconstruction of the mandible using a vascularized free fibular flap through a digital surgical technique in order to restore the patient's facial symmetry and prepare the area for functional restorations. The case illustrates who the free fibular flap graft can be used for satisfactory mandibular reconstruction and restoration of the morphology and functions.

Primary observation of the role of posttranslational modification of dentin sialophosphoprotein (DSPP) on postnatal development of mandibular condyle in mice.

OBJECTIVES: We aimed to observe the posttranslational role of dentin sialophosphoprotein (DSPP) on postnatal development of mandibular condyle in mice. METHODS: To explore the function of full-length DSPP, four groups of mice were employed: (1) wild type (WT) mice; (2)Dspp knockout (Dspp KO) mice; (3) mice expressing the normal DSPP transgene in the Dspp KO background (Dspp KO/normal Tg); (4) mice expressing the uncleavable full-length DSPP in the Dspp KO background (Dspp KO/D452A Tg). Firstly, Plain X-ray Radiography and Micro-computed Tomography were used to observe the condylar morphology changes of Dspp KO/D452A Tg mice in comparison with the other three groups. Then, Hematoxylin & eosin and toluidine blue staining were applied to uncover the histological changes of mandibular condylar cartilage (MCC) of Dspp KO/D452A Tg mice. To explore the function of the NH2-terminal fragments (i.e. DSP/DSP-PG), three groups of mice were employed: (1) WT mice; (2) Dspp KO mice; (3) mice expressing the NH2-terminal fragments of DSPP in the Dspp-null background (Dspp KO/DSP Tg). The former strategies were utilized to examine the differences of condylar morphology and histological structures changes within three groups of mice. RESULTS: Transgenic full-length DSPP partially maintained mandibular condylar morphology and MCC thickness of Dspp KO mice. Transgenic DSP failed to do so, but led to smaller mandibular condyle and disordered cartilage structure. CONCLUSIONS: Our observations provide insight into the role of posttranslational modification of DSPP in the postnatal development of healthy MCC and maintenance of condylar morphology.

Dentin Sialophosphoprotein Deletion Leads to Femoral Head Cartilage Attenuation and Subchondral Bone Ill-mineralization.

Dentin sialophosphoprotein (DSPP), which expresses and synthesizes in odontoblasts of dental pulp, is a critical protein for normal teeth mineralization. Originally, DSPP was identified as a dentin-specific protein. In 2010, DSPP was also found in femoral head cartilage, and it is still unclear what roles DSPP play in femoral head cartilage formation, growth, and maintenance. To reveal biological functions of DSPP in the femoral head cartilage, we examined Dspp null mice compared with wild-type (WT) mice to observe DSPP expression as well as localization in WT mice and to uncover differences of femoral head cartilage, bone morphology, and structure between these two kinds of mice. Expression data demonstrated that DSPP had heterogeneous fragments, expressed in each layer of femoral head cartilage and subchondral bone of WT mice. Dspp null mice exhibited a significant reduction in the thickness of femoral head cartilage, with decreases in the amount of proliferating cartilage cells and increases in apoptotic cells. In addition, the subchondral bone mineralization decreased, and the expressions of vessel markers (vascular endothelial growth factor [VEGF] and CD31), osteoblast markers (Osterix and dentin matrix protein 1 [DMP1]), osteocyte marker (sclerostin [SOST]), and osteoclast marker (tartrate-resistant acid phosphatase [TRAP]) were remarkably altered. These indicate that DSPP deletion can affect the proliferation of cartilage cells in the femoral head cartilage and endochondral ossification in subchondral bone. Our data clearly demonstrate that DSPP plays essential roles in the femoral head cartilage growth and maintenance and subchondral biomineralization.

Fibula osteal flap with proximal peroneal perforator skin paddle for composite oromandibular reconstruction: A case report.

RATIONALE: Cutaneous perforators of peroneal vessels are divided into proximal and distal perforators on the basis of perforator distributions and musculocutaneous or septocutaneous properties. The traditional fibular osteocutaneous free flap is raised over the distal two-thirds of the fibula with a skin paddle based on distal perforators, which is affixed to the posterior crural septum. However, the skin pedicle may not be available due to anatomic variations or intraoperative injuries. Herein, because of the absence of distal perforators, we reserved and expropriated proximal perforators originating from the musculocutaneous branch of the superior part of the peroneal artery before it divided into nutrient and arcuate arteries and successfully harvested a separate osteal fibula and proximal perforator skin paddle with a single vascular pedicle-peroneal vessel. PATIENT CONCERNS: A 62-year-old man with a 6-month history of mandibular swelling and soft tissue invasion was referred to us. DIAGNOSIS: Panoramic radiography and computed tomography showed an irregular radiolucent lesion of the mandibular body, and histopathological analysis confirmed a follicular-pattern ameloblastoma. INTERVENTIONS: The diseased mandible and soft tissue were resected and reconstructed with a vascularized fibular osteal flap with the proximal perforator skin paddle. OUTCOMES: The mandibular contour was successfully restored; the skin paddle in the mouth was in good condition after 8 months of follow-up. LESSONS: The proximal perforator is reliable and practical for supplying a skin paddle and has significant potential for future applications. We recommend reserving the proximal perforator skin paddle as a backup flap when planning to raise a fibula flap, since unavailability or injury of the traditional fibular skin island based on distal perforators occurs frequently. This approach can avoid the exploration for a second donor site, save surgical time, and reduce surgical complexity. Moreover, we anticipate more frequent use of the proximal perforator flap in the future because of its flexibility and large volume, and since it can be combined with the osteal fibula or fibular osteocutaneous flap. However, an understanding of the traits of the proximal perforator and determination of its peroneal origin by computed tomography angiography is crucial for predesigning fibular osteal flaps with a proximal perforator skin paddle.

Haploinsufficiency of Dspp Gene Causes Dentin Dysplasia Type II in Mice.

Dentin dysplasia (DD) and dentinogenesis imperfecta (DGI) patients have abnormal structure, morphology, and function of dentin. DD-II, DGI-II, and DGI-III are caused by heterozygous mutations in the dentin sialophosphoprotein (DSPP) gene in humans. Evidences have shown that loss of function of DSPP in Dspp knockout mice leads to phenotypes similar to DGI-III, and that the abnormal dentinogenesis is associated with decreased levels of DSPP, indicating that DSPP haploinsufficiency may play a role in dentinogenesis. Thus, to testify the haploinsufficiency of Dspp, we used a Dspp heterozygous mouse model to observe the phenotypes in the teeth and the surrounding tissues. We found that Dspp heterozygous mice displayed dentin phenotypes similar to DD-II at the ages of 12 and 18 months, which was characterized by excessive attrition of the enamel at the occlusal surfaces, thicker floor dentin of the pulp chamber, decreased pulp volume, and compromised mineralization of the dentin. In addition, the periodontium was also affected, exhibiting apical proliferation of the junctional epithelium, decreased height and width of the alveolar bone, and infiltration of the inflammatory cells, leading to the destruction of the periodontium. Both the dental and periodontal phenotypes were age-dependent, which were more severe at 18 months old than those at 12 months old. Our report is the first to claim the haploinsufficiency of Dspp gene and a DD-II mouse model, which can be further used to study the molecular mechanisms of DD-II.