Proteoglycans play important roles in regulating osteogenesis. Dentin matrix protein 1 (DMP1) is a highly expressed bone extracellular matrix protein that regulates both bone development and phosphate metabolism. After glycosylation, an N-terminal fragment of DMP1 protein was identified as a new proteoglycan (DMP1-PG) in bone matrix. In vitro investigations showed that Ser89 is the key glycosylation site in mouse DMP1. However, the specific role of DMP1 glycosylation is still not understood. In this study, a mutant DMP1 mouse model was developed in which the glycosylation site S89 was substituted with G89 (S89G-DMP1). The glycosylation level of DMP1 was down-regulated in the bone matrix of S89G-DMP1 mice. Compared with wild type mice, the long bones of S89G-DMP1 mice showed developmental changes, including the speed of bone remodeling and mineralization, the morphology and activities of osteocytes, and activities of both osteoblasts and osteoclasts. These findings indicate that glycosylation of DMP1 is a key posttranslational modification process during development and that DMP1-PG functions as an indispensable proteoglycan in osteogenesis.
The present study aimed to analyze the effects of estrogen deficiency on buccal alveolar bone proper and the periodontal ligament in ovariectomized (OVX) rats, compared with rats that had been subjected to sham treatment. Morphological and histological changes in the periodontium were analyzed using micro‑computed tomography and paraffin sectioning. Sections were stained using hematoxylin and eosin, and tartrate‑resistant acid phosphatase. Expression of receptor activator of nuclear factor‑κB ligand (RANKL), dentin matrix protein 1 C‑terminal (DMP1‑C) and osteopontin (OPN) were analyzed using immunohistochemistry. Histomorphometric analysis of buccal alveolar bone proper samples revealed porotic changes and disorganized bone structure in OVX rats. Furthermore, bone mineral density and pore spacing were significantly lower in OVX rats compared with sham rats. Porosity was significantly higher in OVX rats compared with sham rats (P<0.01). A greater number of osteoclasts were observed along the margins of the buccal alveolar bone proper samples from OVX rats compared with those from the sham rats. Expression of OPN and RANKL was significantly higher, and that of DMP1‑C was significantly lower, in OVX rats compared with sham rats. Ovariectomy‑induced osteoporosis is capable of changing the structure of buccal alveolar bone proper and the periodontal ligament, which is likely to increase the risk of periodontal disease.
Background: The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration. Methods: We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan–Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma). Results: Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2–T4 and stages N0–N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4+ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD. Conclusion: Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.
The aim of the present study was to investigate growth factors release kinetics for the combination of fresh platelet-rich fibrin (F-PRF) and lyophilized PRF (L-PRF) with different ratios to promote bone tissue regeneration. First, we quantified the level of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-AB (PDGF-AB) in vitro and analyzed their release kinetics from F-PRF, L-PRF, and the fresh/lyophilized PRF in different weight ratios (F:L=1:1, 1:3, 1:5). The second experimental phase was to investigate the proliferation and differentiation of bone mesenchymal stem cells (BMSCs) as a functional response to the factors released. To further test the osteogenic potential in vivo, different scaffolds (F-PRF, or L-PRF, or F:L=1:1) were implanted in rabbit cranial bone defects. There was a statistically significant increase in proliferation and differentiation of BMSCs when the culture medium contained different PRF exudates collected at day 14 compared with the negative control group. The results showed that the new bone formation in the fresh/lyophilized PRF (1:1) was much more than that of other groups in defects at both 6 and 12 weeks. Our data suggested growth factor concentration and release kinetics as a consequence of fresh and lyophilized PRF combination, which is an effective way for promoting bone regeneration.
The dynamic changes of the microstructure of alveolar bone during orthodontic tooth movement in rats was explored by employing micro-computed tomography (micro-CT) system and to provide theoretical reference for clinical orthodontic treatment. Ten rats were selected randomly as control among 70 adult female Wistar rats, and the other 60 rats were divided into 25-g and 75-g groups of equal number. Orthodontic appliance with force of 25 g and 75 g was installed to perform the molar mesial movement. Microstructural parameters for trabecular bone mesial to the distobuccal root were evaluated at different time points using micro-CT system. Moreover, distance for mesial movement of the molar were measured. Microstructural parameters for trabecular bone of two groups showed no significant changes from day 0 to day 3 (P>0.05); from day 3 to day 7, bone mineral density (BMD), bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) decreased significantly (P<0.05), whereas trabecular separation (Tb.Sp) and structure model index (SMI) increased significantly (P<0.05); from day 7 to day 14, in 25-g group, BMD, BV/TV and Tb.Th increased significantly (P<0.05), while Tb.Sp and SMI decreased significantly (P<0.05). Correspondingly, in 75-g group, changes of parameters did not carry any statistical significance (P>0.05). Furthermore, the 75-g group showed larger distance than 25-g group only at day 14 (P<0.05). In conclusion, in order to maintain the health of periodontal tissues, adequate time for repair and recovery is needed to ensure reasonable remolding of alveolar bone and healthy movement of the orthodontic tooth.
PurposeTo evaluate the effect of trabecular thickness and trabecular separation on modulating the trabecular architecture of the mandibular bone in ovariectomized rats.Materials and MethodsFourteen 12-week-old adult female Wistar rats were divided into an ovariectomy group (OVX) and a sham-ovariectomy group (sham). Five months after the surgery, the mandibles from 14 rats (seven OVX and seven sham) were analyzed by micro-CT. Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed.ResultsCompared to the sham group, trabecular thickness in OVX alveolar bone decreased by 27% (P = 0.012), but trabecular separation in OVX alveolar bone increased by 59% (P = 0.005). A thickness and separation map showed that trabeculae of less than 100μm increased by 46%, whereas trabeculae of more than 200μm decreased by more than 40% in the OVX group compared to those in the sham group. Furthermore, the OVX separation of those trabecular of more than 200μm was 65% higher compared to the sham group. Bone mineral density (P = 0.028) and bone volume fraction (p = 0.001) were also significantly decreased in the OVX group compared to the sham group.ConclusionsOvariectomy-induced bone loss in mandibular bone may be related to the distributional variations in trabecular thickness and separation which profoundly impact the modulation of the trabecular architecture.
Patients with diabetes tend to have an increased incidence of osteoporosis, which may be associated with hyperglycemia; however, the pathogenic mechanisms governing this interaction remain unknown. The present study sought to investigate whether elevated extracellular glucose levels of bone mesenchymal stem cells (BMSCs) could influence osteoblastic differentiation and whether the intracellular Sonic hedgehog (Shh) pathway could adjust the effects. Furthermore, to verify the results in vivo, a rat tooth extraction model was constructed. BMSCs were incubated in eight types of culture medium, including low glucose (LG), LG + lentivirus (Lenti), LG + Lenti-small interfering RNA (Lenti-siRNA), LG + Lenti-Shh, high glucose (HG), HG + Lenti, HG + Lenti-siRNA and HG + Lenti-Shh. The lentiviral transfection efficiency was observed using a fluorescence microscope; protein and mRNA expression was detected by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The matrix mineralization and alkaline phosphatase (ALP) activity of BMSCs were examined by Alizarin red staining and ALP activity assays, respectively. The expression of osteogenesis-related genes in BMSCs were quantified by RT-qPCR. The alveolar ridge reduction was measured and histological sections were used to evaluate new bone formation in the tooth socket. With high concentrations of glucose, Shh expression, matrix mineralization nodules formation, ALP activity and the levels of bone morphogenic protein 4 (BMP4), bone sialoprotein (BSP) and osteopontin (OPN) expression were greatly reduced compared with LG and corresponding control groups. Whereas activated Shh signaling via Lenti-Shh could increase the number of matrix mineralization nodules, ALP activity, and the expression levels of BMP4, BSP and OPN in BMSCs. Additionally, in vivo assays demonstrated that Lenti-Shh induced additional bone formation. Collectively, the results of the present study indicated that HG inhibited the Shh pathway in osteoblasts and resulted in patterning defects during osteoblastic differentiation and bone formation, while the activation of Shh signaling could suppress these deleterious effects.
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