Juan Dai

Subchondral bone loss following orthodontically induced cartilage degradation in the mandibular condyles of rats

Osteoarthritis (OA) is a degenerative joint disease generally characterized by progressive cartilage degradation and subchondral bone changes. Subchondral bone changes have been proposed to initiate or accompany with cartilage degradation in OA. The purpose of this study was to characterize cartilage damage, subchondral bone remodeling, and the possible mechanism involved in these morphological changes in our reported rat model with OA-like lesions in the mandibular condyle. In experimental groups, the dental occlusion was orthodontically disturbed. By histological analysis, transmission electron microscopy (TEM), micro-CT scanning and serum tests, changes in condylar cartilage and subchondral bone were analyzed at 8 and 12 weeks after treatment. The mRNA and protein levels of bone pro-resorptive and pro-formative factors by chondrocytes were investigated. Increased degraded cartilage areas and obvious cartilage calcification were observed in 8- and 12-week treated (EXP) groups compared to the age-matched controls. Subchondral bone loss, characterized as decreased bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), but increased trabecular separation (Tb.Sp), was observed in the 12-week but not the 8-week EXP group, respectively, versus their age-matched controls. The subchondral bone loss in the 12-week EXP group was accompanied with decreased new bone formation rate, but increased serum carboxy terminal telopeptides (CTXs), and increased osteoclast numbers and proportion of surface area in the subchondral bone regions. Increased mRNA and protein levels of M-CSF, VEGF, RUNX and RANKL/OPG ratio, but decreased OPG, were found in condylar cartilage in the 12-week EXP group versus its age-matched controls, and those of RANKL/OPG ratios were significantly higher in the 12-week EXP group than the 8-week EXP. In addition, increased mRNA levels of VEGF, RUNX and RANKL/OPG ratio, but decreased OPG, were also found in condylar cartilage in the 8-week EXP group versus its age-matched controls (All P<0.05). This study demonstrated that obvious subchondral bone loss followed cartilage degradation in the mandibular condyles in the present rat models and suggested that the imbalance of chondrocyte-secreted regulatory factors within the degraded cartilage may play a role in the osteoclastogenesis, and thus leading to the subchondral bone loss in OA.

Effect of remineralizing agents on white spot lesions after orthodontic treatment: A systematic review

INTRODUCTION White spot lesions are a common complication after orthodontic treatment. The aim of this systematic review was to investigate which remineralizing agents are effective for the treatment of white spot lesions after orthodontic treatment. METHODS According to predetermined criteria, 4 databases were searched for appropriate studies. References of the selected articles and relevant reviews were searched for any missed publications. RESULTS Seven randomized controlled trials were selected as eligible studies, and only qualitative analyses were performed because of the diversity of the interventions and outcome measures. Two studies showed significant effects of 2 different fluoride preparations: one with a small sample size and several methodologic deficiencies, and the other using only nonconventional detection methods (ie, DIAGNOdent pen, KaVo, Biberach, Germany) to assess white spot lesions. Two studies involved casein phosphopeptide-amorphous calcium phosphate, which seemed to be effective for the regression of white spot lesions. However, the statistical analysis in 1 study was based on the tooth surfaces instead of the patient, and the visual examination used in the other study to assess the white spots was not reliable. CONCLUSIONS Based on the literature, there is a lack of reliable evidence to support the effectiveness of remineralizing agents for the treatment of postorthodontic white spot lesions.

Age- and sex-related changes of mandibular condylar cartilage and subchondral bone: A histomorphometric and micro-CT study in rats

OBJECTIVE To quantify the age- and sex-related changes in the rat condylar cartilage and subchondral bone. METHODS SD rats were obtained at the ages of 2, 3, 4, 5, 6 and 7 months. For each sex, the temporomandibular joints tissue blocks from four rats were subjected to histological assessment of cartilage thickness and subchondral bone architecture; for the remaining three rats, the mandibular condyles were delivered for gross measurement and evaluation of the mineralization and architecture properties of the subchondral bone by means of micro-CT. RESULTS Rapid decrease of cartilage thickness but increase of subchondral bone density occurred respectively from 2 to 3 and 3 to 4 months old in female and 2 to 4 and 3 to 5 months old in male (P<0.05), whereas rapid changes of subchondral bone architecture occurred from 3 to 4 months old in both sexes (P<0.05). The significant enlargement of condyle size occurred at 4 or 5 months old in female but at 5 or 6 months in male (P<0.05). CONCLUSION This study demonstrated that the rapid developmental changes of rat condylar cartilage and subchondral bone primarily occurred before 4 months of age, resulting in thinner cartilage but larger and thicker subchondral bone, and they were followed by rapid growth in condylar size. Sex differences were identified that the endochondral ossification of fibrocartilage and formation of subchondral bone were faster in female than in male rats, leading to the earlier enlargement of condyle in female than in male.

Mandibular condylar cartilage response to moving 2 molars in rats.

INTRODUCTION The purpose of this study was to investigate the responses of mandibular condylar cartilage to moving 2 molars in different combinations. METHODS Rats were assigned to male and female control and experimental groups (each, n = 5). Elastic rubber bands were used to move medially the maxillary left and the mandibular right first molars in experimental group I. The same method was used to distally move the maxillary left and the mandibular right third molars, 2 mandibular third molars, and 2 maxillary third molars in experimental groups II, III, and IV, respectively. At the end of the eighth week, all condyles were examined histologically. The areas of histologic change as a percentage of total cartilage area were compared by using the Mann-Whitney U test. RESULTS Cartilage degenerative remodeling was observed in experimental groups II, III, and IV. The percentage areas of degenerative remodeling were higher in female experimental groups II and III than in the female control group, and in female experimental group II than in female experimental group IV and male experimental group II (all, P <0.05). CONCLUSIONS The mandibular condylar cartilage of female rats responded variously to different combinations of molar movement; the most obvious remodeling was observed in groups in which the maxillary left and mandibular right third molars were moved.

Osteochondral angiogenesis in rat mandibular condyles with osteoarthritis-like changes

OBJECTIVE To investigate angiogenesis at the osteochondral junction and changes in expression of pro- and anti-angiogenic factors in rat mandibular condyles with osteoarthritis-like changes. METHODS In order to evoke osteoarthritis-like lesions in mandibular condyles, disordered occlusion was created experimentally in rats. Osteochondral vascularity was assessed histologically at 20 and 24 weeks. Protein and mRNA levels of pro-angiogenic factors including vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and matrix metalloproteases 9 (MMP9), and anti-angiogenic factor chondromodulin-I (CHM-I) were investigated by means of immunohistochemical staining and real-time PCR. RESULTS Osteochondral angiogenesis was demonstrated as increased numbers of vascular channels terminating in the calcified cartilage and non-calcified cartilage in 20- and 24-week experimental groups compared with controls (all P<0.05). In the experimental groups, VEGF, CTGF and MMP9 were highly expressed in the tissues adjacent to the osteochondral junction. However, CHM-I was more expressed in the superior but not deep hypertrophic chondrocytes. Compared to their age-matched controls, the protein levels of VEGF and CTGF were higher in 20-week experimental group, and the protein and mRNA levels of CTGF, MMP-9, and CHM-I increased in the 24-week experimental group (all P<0.05). CONCLUSION In the present rat model, osteochondral angiogenesis was observed in mandibular condyles with osteoarthritis-like changes, accompanied with local upregulation of VEGF, CTGF and MMP9. Although the increase in CHM-I may moderate pro-angiogenic factors effects in the superior cartilage, the deficiency of deep hypertrophic chondrocytes to express CHM-I may permit vascular invasion into condylar cartilage.

Recombinant adeno-associated virus serotype 2 (rAAV2)—An efficient vector for gene delivery in condylar cartilage, glenoid fossa and TMJ disc in an experimental study in vivo

OBJECTIVE To elaborate whether rAAV2 can be used for future TMJ gene therapy, we examined the infection efficiencies of rAAV2 in vitro, and the transgene expression pattern mediated by rAAV2 in glenoid fossa, TMJ disc and condylar cartilage in vivo. MATERIALS AND METHODS Different dosages of rAAV2-eGFP (MOI: 5 x 10(4), 1 x 10(4), 5 x 10(3)) were applied to primary cultured condylar chondrocytes of rats. Infection efficiencies were analysed by FACSCalitur at different time points. Vastatin, a molecule not naturally expressed in TMJ, was used as a reporter for detection of rAAV2 mediated transgene expression in vivo. Thirty SD rats were injected with either rAAV2-sec-Vastatin (experimental group) or rAAV2-eGFP (control group) into both sides of TMJ. They were sacrificed at the indicated time (7, 14, 21, 30 and 60 days of injection) and the TMJ samples were collected for RT-PCR and immunostaining analysis. RESULTS High dosage (MOI 5 x 10(4)) of rAAV2-eGFP can achieve desirable transduction efficiencies in vitro after 5 days. Transgene expression of rAAV-sec-Vastatin persisted for about 21 days in glenoid fossa, around 7 days in TMJ disc and at least 60 days in condylar cartilage in vivo. In condylar cartilage, transgene expression was found in the proliferative layer and chondroblast layer (day 7), chondrocyte layer (day 14), pre-hypertrophic and hypertrophic layer (day 21), hypertrophic layer and deep hypertrophic layer (day 30 and 60). CONCLUSION Recombinant AAV2 could be considered as a promising vector for gene therapy in TMJ which can mediate therapeutic gene expression in glenoid fossa, articular disc and condylar cartilage in vivo.