FAK Promotes Osteoblast Progenitor Cell Proliferation and Differentiation by Enhancing Wnt Signaling

Decreased bone formation is often associated with increased bone marrow adiposity. The molecular mechanisms that are accountable for the negative correlation between bone mass and bone marrow adiposity are incompletely understood. Focal adhesion kinase (FAK) has critical functions in proliferation and differentiation of many cell types; however, its roles in osteoblast lineage cells are largely unknown. We show herein that mice lacking FAK in Osterixâ expressing cells exhibited decreased osteoblast number and low bone mass as well as increased bone marrow adiposity. The decreased bone mass in FAKâ deficient mice was accounted for by decreased proliferation, compromised osteogenic differentiation, and increased adipogenic differentiation of bone marrow Osterixâ expressing cells resulting from downregulation of Wnt/βâ catenin signaling due to the reduced expression of canonical Wnt ligands. In contrast, FAK loss in calvarial preosteoblasts had no adverse effect on their proliferation and osteogenic differentiation and these cells had intact Wnt/βâ catenin signaling. © 2016 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135488/1/jbmr2908_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135488/2/jbmr2908-sup-0001-SuppData-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135488/3/jbmr2908.pd

Tsc1 Regulates the Balance Between Osteoblast and Adipocyte Differentiation Through Autophagy/Notch1/βâ Catenin Cascade

A reduction in trabecular bone mass is often associated with an increase in marrow fat in osteoporotic bones. The molecular mechanisms underlying this inverse correlation are incompletely understood. Here, we report that mice lacking tuberous sclerosis 1 (Tsc1) in Osterixâ expressing cells had a significant decrease in trabecular bone mass characterized by decreased osteoblastogenesis, increased osteoclastogenesis, and increased bone marrow adiposity in vivo. In vitro study showed that Tsc1â deficient bone marrow stromal cells (BMSCs) had decreased proliferation, decreased osteogenic differentiation, and increased adipogenic differentiation in association with the downregulation of Wnt/βâ catenin signaling. Mechanistically, TSC1 deficiency led to autophagy suppression and consequent Notch1 protein increase, which mediated the GSK3βâ independent βâ catenin degradation. Together, our results indicate that Tsc1 controls the balance between osteoblast and adipocyte differentiation of BMSCs. © 2018 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146652/1/jbmr3530-sup-0001-SuppData-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146652/2/jbmr3530_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146652/3/jbmr3530.pd

The concentrations of bone calcium, phosphorus and trace metal elements in elderly patients with intertrochanteric hip fractures

IntroductionTrace metal elements may play a crucial role in bone mineralization and metabolism. However, the quantification of trace element concentrations in human bone tissue has received little attention.Materials and methodsBone tissue samples were collected from 55 elderly patients (15 males and 40 females) with intertrochanteric hip fractures. The calcium, phosphorus, manganese, iron, copper, and zinc concentrations in the cortical bone zone, cancellous bone zone, and junction zone between cortical and cancellous bone were determined by energy-dispersive X-ray fluorescence (EDX). The differences in trace element concentrations in the three regions were compared, and the correlation between gender and bone trace element contents of the bones was analyzed using the Kruskal-Wallis’s test. The correlation between age, body mass index (BMI), and bone calcium, phosphorus concentrations, and trace elements in three bone zones was determined using Spearman correlation analysis.ResultsThe Kruskal-Wallis test showed no difference in bone phosphorus concentration among the three regions. In contrast, the difference in the concentrations of bone calcium and four metal elements was statistically significant (P<0.01). In addition, no statistical differences were observed in the concentrations of trace elements among the three regions in elderly male and female patients. Spearman correlation analysis showed a strong negative correlation between bone calcium and phosphorus in three bone regions (r=-0.999, -0.95, -0.998, P < 0.01) and a significant positive correlation between trace metal elements in the cancellous bone zone. In the junction zone, the BMI showed a strong positive correlation with bone calcium content (r=0.347, P=0.009) and a significant negative correlation with phosphorus content (r=-0.349, P=0.009).ConclusionBone calcium and phosphorus were the main components of hydroxyapatite, and these two elements accounted for the majority of bone mineral salts. Trace metal elements are essential for bone metabolism and specific synergistic interactions. BMI may be associated with bone calcium and phosphorus contents in elderly patients with osteoporosis

Artificial intelligence breast ultrasound and handheld ultrasound in the BI-RADS categorization of breast lesions: A pilot head to head comparison study in screening program

BackgroundArtificial intelligence breast ultrasound diagnostic system (AIBUS) has been introduced as an alternative approach for handheld ultrasound (HHUS), while their results in BI-RADS categorization has not been compared.MethodsThis pilot study was based on a screening program conducted from May 2020 to October 2020 in southeast China. All the participants who received both HHUS and AIBUS were included in the study (N = 344). The ultrasound videos after AIBUS scanning were independently watched by a senior radiologist and a junior radiologist. Agreement rate and weighted Kappa value were used to compare their results in BI-RADS categorization with HHUS.ResultsThe detection rate of breast nodules by HHUS was 14.83%, while the detection rates were 34.01% for AIBUS videos watched by a senior radiologist and 35.76% when watched by a junior radiologist. After AIBUS scanning, the weighted Kappa value for BI-RADS categorization between videos watched by senior radiologists and HHUS was 0.497 (p < 0.001) with an agreement rate of 78.8%, indicating its potential use in breast cancer screening. However, the Kappa value of AIBUS videos watched by junior radiologist was 0.39, when comparing to HHUS.ConclusionAIBUS breast scan can obtain relatively clear images and detect more breast nodules. The results of AIBUS scanning watched by senior radiologists are moderately consistent with HHUS and might be used in screening practice, especially in primary health care with limited numbers of radiologists

NF-kappa B mediated Up-regulation of CCCTC-binding factor in pediatric acute lymphoblastic leukemia

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most frequently occurring malignant neoplasm in children. Despite advances in treatment and outcomes for ALL patients, the pathogenesis of the disease remains unclear. Microarray analysis of samples from 100 Chinese children with ALL revealed the up-regulation of CTCF (CCCTC binding factor). CTCF is a highly conserved 11-zinc finger protein that is involved in many human cancers; however, the biological function of CTCF in pediatric ALL is unknown. METHODS: The expression patterns of CTCF were evaluated in matched newly diagnosed (ND), complete remission (CR), and relapsed (RE) bone marrow samples from 28 patients. The potential oncogenic mechanism of CTCF and related pathways in leukemogenesis were investigated in leukemia cell lines. RESULTS: We identified significant up-regulation of CTCF in the ND samples. Importantly, the expression of CTCF returned to normal levels after CR but rebounded in the RE samples. In the pre-B ALL cell line Nalm-6, siRNA-mediated silencing of CTCF expression promoted cell apoptosis and reduced cell proliferation; accordingly, over-expression of a cDNA encoding full-length CTCF protected cells from apoptosis and enhanced cell proliferation. Furthermore, inhibition or activation of the nuclear factor-kappa B (NF-κB) pathway resulted in marked variations in the levels of CTCF mRNA and protein in leukemic cells, indicating that CTCF may be involved downstream of the NF-κB pathway. Moreover, inhibition of the NF-κB pathway increased cell apoptosis, which was partially rescued by ectopic over-expression of CTCF, suggesting that CTCF may play a significant role in the anti-apoptotic pathway mediated by NF-κB. CONCLUSIONS: Our results indicate that CTCF serves as both an anti-apoptotic factor and a proliferative factor in leukemic cells. It potentially contributes to leukemogenesis through the NF-κB pathway in pediatric ALL patients