INTRODUCTION It has been known for many years that tendon‐attached bone is rough and bump, and that patients with hypophosphatemic rickets (such as DMP1 mutations) develop osteosclerosis in the tendon‐attached area. The goal of this study was to test whether tendon directly forms bone and how hypophosphatemia initiates the onset of osteosclerosis in a Dmp1 KO mouse (a hypophosphatemic rickets model) using cell lineage tracing and multiple imaging techniques. METHODS We generated a chondrocyte tracing mouse line (Col 10a1‐Cre;R26R tomato) and a tendon tracing mouse line (Scx‐CreERT2;R26R tomato) with and without a Dmp1 KO background, plus a high Pi rescue diet treatment for seven weeks. RESULTS Our key findings were: 1) the non‐tendon attached bone cells were negative in both tracing lines; 2) cells in the tendon‐attached bone were Scx+ but Col X − ; 3). In the Dmp1 KO mice, tendon‐attached bone volume sharply increased, in which there were more EdU+ bone cells (i.e., more cell proliferation) with high expression levels of bone markers such as Runx2 and β‐catenin; and 4) a high Pi diet greatly improved the above phenotypes. CONCLUSION Tendon (an avascular tissue) directly forms bone cells in the tendon‐bone joint area, which is rough and porous compared to non‐tendon attached bones. Osteosclerosis in Dmp1 KO (a hypophosphatemia rickets model) is caused by accelerated cell transdifferentiation from tendon to bone due to hypophosphatemia. Support or Funding Information U.S. National Institutes of Health grants to J.Q.F. (R01DE025014 and DE025659)
Abstract Objectives: The purpose of this study was to investigate short- and long-term postoperative changes of both morphology and transverse stability in mandibular ramus after intraoral vertical ramus osteotomy (IVRO) in patients with jaw deformity using three-dimensional (3D) orthognathic surgery planning treatment software for measurement of distances and angles. Study Design: This retrospective study included consecutive patients with skeletal Class III malocclusion who had undergone intraoral vertical ramus osteotomy and computed tomography images before (T0), immediately after (T1), and one year after (T2) surgery. Reference points, reference lines and evaluation items were designated on the reconstructed 3D surface models to measure distances, angles and volume. The average values at T0, T1, T2 and time-dependent changes in variables were obtained. Results: After surgery, the condylar length, ramal height, mandibular body length and mandibular ramus volume were significantly decreased ( P < .01), while clinically insignificant change was observed from T1 to T2. The angular length was increased immediately after surgery ( P < .05), but it was decreased 1 year after surgery ( P < .05). Lateral ramal inclination showed significant increase after surgery ( P < .05) and maintained at T2. Conclusion: Changes in the morphology of the mandibular ramus caused by IVRO do not obviously bring negative effect on facial appearance. Furthermore, despite position and angle of mandibular ramus changed after IVRO, good transverse stability was observed postoperatively. Therefore, IVRO technique can be safely used without compromising esthetic results.
The cause of Alzheimer’s disease, the most common type of dementia today, is still unclear, and in current research, there are no drugs that work relatively well. Therefore, the study for new drugs to treat Alzheimer’s disease is an urgent research need. Research on the improvement of Alzheimer’s disease with extracts of Xanthoceras sorbifolia has been increasing in recent years, but the mechanism is not fully understood. The experiments were conducted to validate the model and analyze the treatment effect through D-galactose and Aβ25–35 induced dementia model mice, using the Morris water maze, to detect the learning behavior and brain tissue section to observe the hippocampal tissue structure of mice. We performed a nontargeted metabolomic analysis of the urine obtained from different groups of mice using gas chromatography-mass spectrometry. Fourteen potential biomarkers were identified in the mice’s urine, outlining five metabolic pathways of interest. It was shown that the extracts of Xanthoceras sorbifolia may exert protective effects on mice in dementia models through energy metabolism, neuroinflammation, and antioxidants. This study reveals the potential pathogenesis of Alzheimer’s disease and the possible therapeutic mechanism of Xanthoceras sorbifolia, suggests relevant biomarkers, and provides an additional basis for the clinical application of Xanthoceras sorbifolia.
Aim at the two problems in the field of traditional Chinese medicine (TCM) mechanism elucidation, one is the lack of detailed biological processes information, next is the low efficient in constructing network models, we constructed an auxiliary elucidation system for the TCM mechanism and realize the automatic establishment of biological network model. This study used the Entity Grammar Systems (EGS) as the theoretical framework, integrated the data of formulae, herbs, chemical components, targets of component, biological reactions, signaling pathways and disease related proteins, established the formal models, wrote the reasoning engine, constructed the auxiliary elucidation system for the TCM mechanism elucidation. The platform provides an automatic modeling method for biological network model of TCM mechanism. It would be benefit to perform the in-depth research on TCM theory of natures and combination and provides the scientific references for R&D of TCM.
Objective:To study the expression of BMP during osteogenesis of autogenesis of minimal morselized bone (AMMB) and its mechanism. Method:Forty eight rabbits were divided into 2 groups equally and randomly :bulk bone was harvested from left ilium of rabbits. In group A(24 rabbits): bulk bone was turned into morselized bone (0.3 ×0.5×1.0)cm 3;in group B(24 rabbits): bulk bone was planted in right musculus glutaeus maximus .Sample was havested at the 1 st , 3 rd , 5 th , 7 th , 9 th ,11 th , 14 th , 21 st , 28 th day after operation. Then it was tested by histological method, immunohistological chemistry and ISH. All the result was analyzed by computer. Result: (1) During ectopic osteogenesis of AMMB was absorbed quickly and replaced totally, compared with group B,the concentration of BMP in group A was higher, (2) BMP existed and played the key role during the whole course of osteogenesis. (3) AMMB may be the origin of osteogenesis. Conclusion:The ectopic osteogenesis of AMMB is better than that of bulk bone, and BMP is main factor during osteogenesis.
Recent studies suggest that tendons play a critical role in the initiation of bone ridges by transducing SCX/BMP4 signaling to osteochondroprogenitors, although tendons are mainly considered to simply control skeletal movement and joint stabilization. Currently, intramembranous ossification and endochondral ossification are thought to be the only osteogenic mechanisms. However, the rough bone ridges appear different from the surrounding smooth bone structure. The aim of this study is to test a hypothesis: tendons directly form bone ridges (a third type of bone) by multiple cell transdifferentiation steps: tendon-fibroblast-bone cells. To test this hypothesis, we used the humerus bone ridge (deltoid tuberosity) as a model. We injected Alizarin Red to 2.3kb Col 1-GFP (reflecting bone cells) mice 4 hours prior to harvesting, followed by imaging of the non-decalcified bone to analyze the mineralization status of the humerus bone (including the deltoid tuberosity). In contrast to a monolayer of GFP+ bone cells in the periosteum-formed bone (PFB), there were multilayers of GFP+ fibroblast-like bone cells between the tendon and deltoid tuberosity beneath, indicating a cell transdifferentiation from tendon to bone (Fig a). The H&E staining showed a gradual transdifferentiation from tendon cells to fibroblast-like cells to bone cells with a different cell distribution from PFB (Fig b). The quantitative uCT-analysis displayed a low bone mineral density (BMD, Fig c, left). The cell lineage tracing data (using a tendon specific ScxCreERT2-R26-tdtomato line induced at P3 by one-time injection of tamoxifen) showed a rapid expansion of tendon-formed bone (TFB) cells from few at P9 to many TFB cells at P33, and maturation at P60 (Fig c). These TFB cells expressed high levels of periostin (tendon marker), aggrecan (cartilage marker), RUNX2 and SOST (two bone markers; Fig d, upper panels), which were sharply reduced when DTA (diphtheria toxin subunit A) was activated in the Scx-Cre+ cells at P3 and harvested at p30 (Fig d, lower panel). Finally, we stabilized β-catenin in Scx expressing cells (β-cateninfx(exon3)/fx(exon3)) at P3 and harvested at P60. These mice displayed an expanded deltoid tuberosity mass and sharply increased Scx+ bone cells (Fig e, lower panels). Based on the data above, we proposed that tendon cells directly form bone ridges by a continuous cell transdifferentiation from tendon cells to fibroblast-like cells, and then to bone cells. These TFB cells display a distinct feature from conventional bone, including a low BMD, a mixture profile of extracellular matrix proteins that are normally expressed in tendon, cartilage and bone (Fig f). This novel discovery on the broader roles of tendon explains why bone ridges embrace different features from conventional bone and makes the tendon-bone interface a mineralized continuum rather than a simple attachment.
As the initial part in the development of osteoarthritis (OA), subchondral bone sclerosis has been considered to be initiated by excess mechanical loading and proven to be correlated to other pathological changes. Sclerostin, which is an essential mechanical stress response protein, is encoded by the SOST gene. It is expressed in osteocytes and mature chondrocytes and has been proven to be closely correlated to OA. However, the relationship and mechanism between the SOST gene and the development of OA remain unclear. The aim of the present study was to investigate the role of the SOST gene in OA pathogenesis in the subchondral bone. A knee anterior cruciate ligament transection (ACLT) mouse osteoarthritis (OA) model on SOST-knockout (SOST KO) and wild-type (WT) mice was established. The pathogenic and phenotypic changes in the subchondral bone were investigated by histology, micro-CT, immunohistochemistry, TRAP staining, Masson staining, and Toluidine blue staining. It was found that sclerostin expression decreased in both the calcified cartilage and mineralized subchondral structures during the development of OA. Joint instability induced a severe cartilage degradation phenotype, with higher OARSI scores in SOST KO mice, when compared to WT mice. SOST KO mice with OA exhibited a higher BMD and BV/TV ratio, as well as a higher rate of bone remodeling and TRAP-positive cell number, when compared to the WT counterparts, but the difference was not significant between the sham-operation groups. It was concluded that loss of sclerostin aggravates knee OA in mice by promoting subchondral bone sclerosis and increasing catabolic activity of cartilage.
Objective This study was designed to understand the situation of quality of the infectious diseases reports handed on directly through network and failure to report statutory infectious diseases by hospitals in Tengzhou, so as to provide scientific evidence for disease control and prevention. Methods By adopting stratified sampling, investigation of statutory infectious diseases registered and reported by 35 medical institutes in 2004 was conducted. Statistic analysis of epidemiology was employed for data processing. Results The intact rate of infectious disease case reports handed on directly through network was 87.20% and the rate of timely report was70.70%, while the failure to report statutory infectious diseases by medical institutes was 17.50%. Conclusion Through direct network report, intact rate of report and the rate of timely report for statutory infectious diseases were both increased compared with the previous ones. However, the administration of infectious diseases by each medical institute was not balanced. As for clinical doctors in some hospitals, their consciousness to report statutory infectious diseases and awareness of report were not strong enough. Therefore, it is necessary to reinforce their legal consciousness and service quality, and to enhance the report and administration of epidemic situation.
American alligators ( Alligator mississippiensis ) are a large crocodilian living in the southeastern United States of America. Compared to mammals, they have an extended growth period after reaching adulthood. Evolutionarily, they are also one of few vertebrates that have survived long geological periods with conservative morphology. Thus among many aspects related to the growth, development, and physiological adaptions of this long surviving species, the bone biology is interesting in terms of extended bone growth and maintenance, and especially the morphology and behavior of the osteons, the fundamental functional unit in the cortical bone. In this study, alligator bones were analyzed to visualize reptilian osteocytes and compare them to those of mice, the most commonly used mammalian model in bone biology and pharmaceutical studies. In the femora of a one‐year‐old alligator, the osteon structure of the cortical bone was studied to reveal the density and structure of osteons, as well as the morphology of osteocytes, using confocal imaging by Fluorescein Iso‐Thio‐Cyanate sample preparation and staining, and osteocyte morphology was visualized using acid‐etch SEM. Results demonstrated that in this relatively fast growing individual, there were few osteon‐like structures lined along the periosteum and endosteum, indicating a slow rate of bone remodeling. Compared to osteocytes in mice, osteocytes in the alligator specimen were irregular in shape and less evenly distributed, and had fewer dendrites. This study demonstrated the morphology of alligator osteocytes for the first time. The findings indicate that there are significant differences in bone morphology and physiology at the microstructural level between reptiles and mammals; the implications in our understanding of bone biology is yet to be fully understood. This study also suggests that American alligators will be an idea model for studying bone development, adaptation, and evolution at the pre‐mammalian stage. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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