Osteocytes have recently been identified as a new regulator of bone remodeling, but the detailed mechanism of their differentiation from osteoblasts remains unclear. The purpose of this study is to identify cell cycle regulators involved in the differentiation of osteoblasts into osteocytes and determine their physiological significance. The study uses IDG-SW3 cells as a model for the differentiation from osteoblasts to osteocytes. Among the major cyclin-dependent kinases (Cdks), Cdk1 is most abundantly expressed in IDG-SW3 cells, and its expression is down-regulated during differentiation into osteocytes. Inhibition of CDK1 activity reduces IDG-SW3 cell proliferation and differentiation into osteocytes. Osteocyte and Osteoblast-specific Cdk1 knockout in mice (Dmp1-Cdk1KO ) results in trabecular bone loss. Pthlh expression increases during differentiation, but inhibiting CDK1 activity reduces Pthlh expression. Parathyroid hormone-related protein concentration is reduced in the bone marrow of Dmp1-Cdk1KO mice. Four weeks of Parathyroid hormone administration partially recovers the trabecular bone loss in Dmp1-Cdk1KO mice. These results demonstrate that Cdk1 plays an essential role in the differentiation from osteoblast to osteocyte and the acquisition and maintenance of bone mass. The findings contribute to a better understanding of the mechanisms of bone mass regulation and can help develop efficient therapeutic strategies for osteoporosis treatment.
Osteoblasts , Osteocytes , Animals , Mice , Cell Differentiation/genetics , Cell Proliferation , Osteoblasts/metabolism , Osteocytes/metabolism , Parathyroid Hormone/pharmacology , Parathyroid Hormone/metabolism
Objective:To explore the risk factors for urinary tract infection (UTI) after a spinal cord injury (SCI).Methods:The medical records of 403 SCI patients were analyzed retrospectively. They were divided into UTI group and no-UTI group according to whether they had a UTI at admission. Gender, age, cause of injury, injury level of the spinal cord, voluntary anal contraction, time from injury to admission, American Spinal Injury Association (ASIA) grade, axillary temperature at admission, complications at admission (diabetes, hypertension, fracture of the pelvis, pressure sores or anemia), white blood cell count and urinary bacteria were compared between the two groups. Binary logistic regression was used to highlight the risk factors for a UTI after an SCI.Results:Of the 354 patients included in the final analysis, 62 (17.51%) had a UTI at admission. The regression showed that UTI after an SCI was closely related to an inability to voluntarily contract the anus, anemia, elevated white blood cell count and a high level of bacteria in the urine.Conclusions:Inability to contract the anus, fever, anemia and an elevated white blood cell count are independent indicators of a UTI after an SCI. A temperature ≥37.3°C is a simple indicator of a concentration of bacteria in the urine ≥1266/μL.
Objective:To explore the risk factors for lower extremity deep vein thrombosis (DVT) in patients with a spinal cord injury (SCI).Methods:The medical records of 276 hospitalized SCI patients were analyzed retrospectively. They were divided into a DVT group ( n=63) and a no-DVT group ( n=213). Gender, age, blood type, smoking history, surgical history, the time from SCI to admission, cause of SCI, fracture, SCI segments, American Spinal Cord Injury Association grade and complications were compared between the two groups. Binomial logistic regression was used to isolate the risk factors for lower extremity DVT among such patients. Results:Among 84% of the 63 with a lower extremity DVT, it was a calf muscle venous thrombosis. Anemia, hyponatremia and time from SCI to admission (which ranged from 74 to 195 days) were the most serious DVT risk factors.Conclusions:SCI patients are of high risk for DVT, with anemia and hyponatremia being independent risk factors.
Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is a critical process for proper skeletal development and acquisition/maintenance of bone mass. However, since this regulatory mechanism has not yet been fully elucidated, the treatment of severe osteoporosis and fractures is a challenge. Here, through a comprehensive analysis of gene expression during the differentiation of MSCs into osteoblasts, we show that the forkhead transcription factor Foxf2 is a crucial regulator of this process. Foxf2 expression transiently increased during MSC osteoblastic differentiation. Overexpression of Foxf2 in MSCs inhibited osteoblastic differentiation, and conversely, knockdown of Foxf2 expression promoted this process. Osteoprogenitor-specific Foxf2 knockout mice developed a high bone mass phenotype due to increased bone formation. RNA-seq analysis and molecular experiments revealed that Foxf2 regulation of bone formation is mediated by Wnt2b. Knockdown of Foxf2 in mouse femurs enhanced bone regeneration in vivo. FOXF2 expression was correlated with hip bone mineral density in postmenopausal women with low bone mass. Finally, inhibition of FOXF2 promoted osteoblastic differentiation of human MSCs. This study uncovers a critical role of Foxf2 in the differentiation of MSCs into osteoblasts and provides insight into the pathogenesis associated with bone-related diseases such as osteoporosis and nonunion after fracture.
Osteoporosis , Wnt Signaling Pathway , Animals , Cell Differentiation/genetics , Female , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Glycoproteins/metabolism , Mice , Mice, Knockout , Osteoblasts/metabolism , Osteogenesis/genetics , Osteoporosis/genetics , Wnt Proteins/metabolism , beta Catenin/genetics , beta Catenin/metabolism
Objective:To examine the risk factors for neuropathic pain (NP) after a spinal cord injury (SCI).Methods:A total of 115 patients with a SCI were analyzed retrospectively. They were divided into an NP group of 53 and a non-NP group of 62 according to the occurrence of NP. Gender, age, length of stay, occupation, level of education, cause of injury, spinal fracture, degree of SCI, the injury′s plane and complications at admission (diabetes, hypertension, anemia, venous thrombosis, pressure sores, urinary tract infection or hypoproteinemia) were recorded. T-tests and chi-squared tests were used to compare those factors between the two groups, and multivariate logistic regressions were evaluated to identify the risk factors for NP.Results:Twenty-three of the 53 cases of NP (43%) had developed within 1 month of the SCI. Thirty-seven (75%) experienced pain below the plane of the SCI. The main features reported were squeezing (34%) and numbness (26%). The multivariate logistic regression showed that the occurrence of NP was most strongly related to gender (women being particularly at risk) and venous thrombosis at admission.Conclusions:Women are at particular risk of feeling NP after an SCI, and venous thrombosis is an independent risk factor. NP should be diagnosed and treated quickly to reduce the negative impact on patients′ life quality.
