Objective:To investigate the feasibility of establishing a canine model of lumbar intervertebral disc degeneration through the application of cumulative axial load and a six-phase combined motion on the vertical sitting dog's lumbar spine.Methods:Twenty adult female grass dogs, each weighing 10.0±0.5 kg, were randomly divided into two groups, with 10 dogs in each group. In the model group, dogs were secured to an exercise machine in a vertical position, and six phases of lumbar spine movement (flexion and extension, left and right lateral flexion, left and right rotation, 45° each) were combined with a specific number of cycles under continuous axial load (245 N). In the control group, dogs were secured to the exercise machine in a vertical position without any intervention. Radiographic examinations were performed before and after 20,000, 50,000, 100,000, and 150,000 compound exercises in the model group. The disc height index (DHI) was measured through lateral X-ray, and MRI T2-mapping was used for quantitative analysis of intervertebral disc degeneration. When intervertebral disc degeneration was evident on MRI T2-weighted imaging (modified Pfirrmann system > Grade V), the combined motion was halted. Micro-CT quantitative analysis of bone mineral density (BMD) in the upper and lower endplates, trabecular bone structure, and histological staining (HE staining, "O" staining, Sirius red staining) were employed to verify and assess the degree of intervertebral disc degeneration.Results:After 50,000 compound exercises, mild degeneration of the intervertebral discs at L 6-7 and L 7S 1 was observed on T2-weighted imaging. With the accumulation of exercise load, the degree of degeneration progressively increased, reaching a moderate degree of degeneration after 100,000 composite exercises, and DHI began to decrease. Mild degeneration was also observed in the upper L 5-6 intervertebral disc. When the cumulative exercise volume reached 150,000 repetitions, the height of intervertebral spaces in the L 5-6, L 6-7, and L 7S 1 segments further decreased, and the intervertebral discs exhibited severe degeneration (improved Pfirrmann grading system Grades IV-VI). The upper L 4-5 intervertebral discs also displayed mild degeneration. Histological scores were as follows: L 5-6 (8.2±0.8), L 6-7 (9.5±0.7), and L 7S 1 (10.3±0.5), indicating a degree of degeneration in the order of L 5-6

Objective:To discuss hypertension situations of 40-79 years old residents with different glucose metabolic status in Guiyang urban area under the new hypertension diagnostic criteria proposed by American College of Cardiology/American Heart Association (ACC/AHA) in 2017 and provide a clue for diagnostic criteria and treatment strategy of hypertension.Methods:10 140 residents in 40-79 years old in Risk Evaluation of cAncers in Chinese diabeTic Individuals: a IONgitudinal (REACTION) Study Research Guiyang Sub-center were conducted retrospective analysis. According to medical history of diabetes and oral glucose tolerance test results, these residents were divided into normal glucose group, impaired fasting glucose(IFG) group, impaired glucose tolerance (IGT) group, IFG+ IGF group, previous diagnostic diabetes group and newly diagnosed diabetes group. Hypertension situation of residents with different glucose metabolic status under the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), and Hypertension Guide of ACC/AHA in 2017 were calculated.Results:Under JNC 7 criteria, hypertension′s standardized prevalence rate of normal blood glucose people, prediabetes patients, and diabetes patients in 40-79 years old respectively reached 8.19%, 9.57%, and 8.19%. Under ACC/AHA 2017 criteria, hypertension′s standardized prevalence rate respectively reached 20.27%, 16.35%, and 11.59%. By contrast, the most obvious increase of hypertension′s prevalence rate was in the normal blood glucose group and IGT group. Newly increased hypertension patients reached 1 739. Among them, 25.8% required antihypertensive drugs for treatment. According to the 6th demographic census data of Guizhou Province in 2010, it was estimated that newly increased hypertensive patients aged 40-79 years in prediabetes patients reached 123 000, among them, 20 000 required treatment. Newly increased hypertensive patients aged 40-79 years in diabetes patients reached 68 000, among them, 21 000 required treatment.Conclusions:ACC/AHA Hypertension Guide in 2017 will obviously increase hypertension′s prevalence rate of people with different glucose metabolic status in 40-49 years old. The treatment ratio of hypertension groups with diabetes and prediabetes is considerably high. As a result, social medical burdens is going to aggravate.

Objective:To explore whether metabolically healthy obesity(MHO) is a healthy state by observing the incidence of metabolic syndrome(MS) including its components and cardiovascular disease(CVD) in this population.Methods:In 2011, a cohort of 10 140 residents aged 40-79 years old was selected with cluster sampling in the Guiyang urban area. Fasting plasma glucose(FPG), blood lipids, and blood pressure were examined to assess their metabolic status. Height and weight were also measured. Among them, 1 299 metabolically healthy subjects were divided into 3 groups according to body mass index, namely metabolically healthy normal weight(MHNW), metabolically healthy overweight(MHOW), and MHO. Three groups were reassembled in 2014, and finally a total of 966 subjects with baseline and complete follow-up data were included in the analysis. The relationship between MS and its components, and the incidence of CVD were compared among the three groups.Results:(1) After an average follow-up of 3 years, 47.77% of the MHO population transformed into a metabolically unhealthy state. There was no significant difference in the incidence of MS components among the three groups( P>0.05), but there was a significant difference in the incidence of MS( P<0.05); (2) There was no significant difference in the incidence of CVD among the three groups after 3 years of follow-up. Logistic regression was used to analyze the risk factors of CVD in the three groups. Taking the MHNW as the control group, after adjusting for age, gender, FPG, blood lipids, and blood pressure, the risk ratio of the MHOW group was 0.941(0.661-1.202), and MHO group was 0.974(0.702-1.291). Conclusions:After 3 years of follow-up, although the risk of CVD in the MHO population did not increase significantly, the incidences of MS, triglycerides, and FPG abnormality increased compared with the normal people, suggesting that the MHO is not a " stable" healthy state.

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1⁺ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1⁺ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1⁺ cells in PDL cells. The behavior of PRX1⁺ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1⁺ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1⁺ cells; during transplanted teeth PDL reconstruction, PRX1⁺ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1⁺ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.
Animals ; Cell Differentiation ; Mesenchymal Stem Cells ; Mice ; Molar ; Osteogenesis/physiology* ; Periodontal Ligament

Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
Mice ; Animals ; Hedgehog Proteins/genetics* ; Receptors, G-Protein-Coupled/metabolism* ; Cilia/metabolism* ; Cartilage/metabolism* ; Regeneration