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Nina Bon, Giulia Frangi, Sophie Sourice, Jérôme Guicheux, Sarah Beck-Cormier, Laurent Beck
OBJECTIVE: The canonical role of the bone-derived fibroblast growth factor 23 (Fgf23) is to regulate the serum inorganic phosphate (Pi) level. As part of a feedback loop, serum Pi levels control Fgf23 secretion through undefined mechanisms. We recently showed in vitro that the two high-affinity Na+ -Pi co-transporters PiT1/Slc20a1 and PiT2/Slc20a2 were required for mediating Pi-dependent signaling. Here, we addressed the contribution of PiT1 and PiT2 to the regulation of Fgf23 secretion...
February 26, 2018: Molecular Metabolism
Matthew T Drake, Jennifer S Fenske, Frank A Blocki, Claudia Zierold, Natasha Appelman-Dijkstra, Socrates Papapoulos, Sundeep Khosla
Sclerostin is a 190 amino acid protein secreted primarily by osteocytes. It was initially identified due to mutations in the SOST gene associated with high bone mass phenotypes. Much recent work has sought to determine the importance of sclerostin across an array of conditions which affect the human skeleton. However, accurate measurement of sclerostin from serum and plasma sources remains a significant impediment, with currently available commercial assays showing marked differences in measured sclerostin values...
March 14, 2018: Bone
Ji-Hye Kim, Ae Ri Kim, Yun Hui Choi, Aeryun Kim, Yongsung Sohn, Gye-Hyeong Woo, Jeong-Heon Cha, Eun-Jung Bak, Yun-Jung Yoo
BACKGROUND: Periodontitis is an infectious disease that manifests as alveolar bone loss surrounding the roots of teeth. Diabetes aggravates periodontitis-induced alveolar bone loss via suppression of bone formation. Intermittent parathyroid hormone (PTH) administration displays an anabolic effect on bone. In this study, we investigated the effect of intermittent PTH administration on alveolar bone loss in type 1 diabetic rats with periodontitis. METHODS: Rats were divided into control (C), periodontitis (P), periodontitis treated with PTH (P + PTH), diabetes with periodontitis (DP), and diabetes with periodontitis treated with PTH (DP + PTH) groups...
March 15, 2018: Journal of Translational Medicine
Melda Onal, Alex H Carlson, Jeff D Thostenson, Nancy A Benkusky, Mark B Meyer, Seong M Lee, J Wesley Pike
Fibroblast growth factor 23 (FGF23) production is regulated by both calciotropic hormones and inflammation. Consistent with this, elevated FGF23 levels are associated with inflammatory markers as well as parathyroid hormone (PTH) in various disease states, including chronic kidney disease (CKD). However, the molecular mechanisms underpinning Fgf23 transcription in response to these regulators are largely unknown. We therefore utilized chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) data from an osteocyte cell line to identify potential regulatory regions of the Fgf23 gene...
January 2018: JBMR Plus
Jonas Lorenz, Alica Kubesch, Sarah Al-Maawi, Frank Schwarz, Robert A Sader, Markus Schlee, Shahram Ghanaati
OBJECTIVES: The aim of the present study was the histological investigation of an allogeneic spongious bone block for horizontal and vertical ridge augmentation in humans. The amount of new bone, soft tissue, and residual bone substitute were histomorphometrically assessed after a mean healing period of 6 months. MATERIALS AND METHODS: Fourteen patients received augmentation with an allogeneic spongious bone block (Tutobone® , Tutogen Medical, Neunkirchen, Germany)...
March 9, 2018: Clinical Oral Investigations
David E Leaf, Edward D Siew, Michele F Eisenga, Karandeep Singh, Finnian R Mc Causland, Anand Srivastava, T Alp Ikizler, Lorraine B Ware, Adit A Ginde, John A Kellum, Paul M Palevsky, Myles Wolf, Sushrut S Waikar
BACKGROUND AND OBJECTIVES: Dysregulated mineral metabolism is a common and potentially maladaptive feature of critical illness, especially in patients with AKI, but its association with death has not been comprehensively investigated. We sought to determine whether elevated plasma levels of the osteocyte-derived, vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23), are prospectively associated with death in critically ill patients with AKI requiring RRT, and in a general cohort of critically ill patients with and without AKI...
March 8, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Yung-Ching Chen, King-Chuen Wu, Bu-Miin Huang, Edmund Cheung So, Yang-Kao Wang
Midazolam, a benzodiazepine derivative, is widely used for sedation and surgery. However, previous studies have demonstrated that Midazolam is associated with increased risks of congenital malformations, such as dwarfism, when used during early pregnancy. Recent studies have also demonstrated that Midazolam suppresses osteogenesis of mesenchymal stem cells (MSCs). Given that hypertrophic chondrocytes can differentiate into osteoblast and osteocytes and contribute to endochondral bone formation, the effect of Midazolam on chondrogenesis remains unclear...
March 7, 2018: Journal of Cellular and Molecular Medicine
Tomoki Nakashima
Recent studies of mouse genetics and human gene mutations has greatly contributed to clarifying the molecular mechanism of bone metabolism. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication among bone component cells such as osteoclasts, osteoblasts, osteocytes and endothelial cells...
2018: Clinical Calcium
Seiji Fukumoto
Osteocytes have several functions such as sensing mechanical load to bone and regulating osteoclastic bone resorption. In addition, osteocytes secrete several humoral factors that affect bone and other organs. FGF23 produced by osteocytes works as a hormone that reduces serum phosphate level. Sclerostin suppresses bone formation by inhibiting Wnt signals. Drugs that inhibit the activities of these factors are now under investigation as new therapeutic measures.
2018: Clinical Calcium
Tao Qiu, Janet L Crane, Liang Xie, Lingling Xian, Hui Xie, Xu Cao
Parathyroid hormone (PTH) regulates bone remodeling by activating PTH type 1 receptor (PTH1R) in osteoblasts/osteocytes. Insulin-like growth factor type 1 (IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Here we report that PTH and IGF-I synergistically enhance osteoblast-to-osteocyte differentiation. We identified that a specific tyrosine residue, Y494, on the cytoplasmic domain of PTH1R can be phosphorylated by insulin-like growth factor type I receptor (IGF1R) in vitro...
2018: Bone Research
Estee L George, Sharon L Truesdell, Spencer L York, Marnie M Saunders
Researchers have been using lab-on-a-chip systems to isolate factors for study, simulate laboratory analysis and model cellular, tissue and organ level processes. The technology is increasing rapidly, but the bone field has been slow to keep pace. Novel models are needed that have the power and flexibility to investigate the elegant and synchronous multicellular interactions that occur in normal bone turnover and in disease states in which remodeling is implicated. By removing temporal and spatial limitations and enabling quantification of functional outcomes, the platforms should provide unique environments that are more biomimetic than single cell type systems while minimizing complex systemic effects of in vivo models...
February 27, 2018: Experimental Cell Research
Pratheep Sandrasaigaran, Satar Jabbar Rahi Algraittee, Azfar Rizal Ahmad, Sharmili Vidyadaran, Rajesh Ramasamy
Mesenchymal stem cells (MSCs) exert potent immuno-regulatory activities on various immune cells and also differentiate into various mesodermal lineages besides retaining a distinct self-renewal ability. Such exclusive characteristics had enabled MSCs to be recognised as an ideal source for cell-based treatment in regenerative medicine and immunotherapy. Thus, considering MSCs for treating degenerative disease of organs with limited regenerative potential such as cartilage would serve as an ideal therapy. This study explored the feasibility of generating human cartilage-derived MSCs (hC-MSCs) from sports injured patients and characterised based on multipotent differentiation and immunosuppressive activities...
March 1, 2018: Cytotechnology
Pei Ye, Xueping Ke, Xuehui Zang, Hui Sun, Zhixing Dong, Jun Lin, Lihui Wang, Wenzhou Liu, Guiqiang Miao, Yongtao Tan, Weilai Tong, Haichang Xiao, Lihua Gao
OBJECTIVE: MicroRNAs (miRNAs) play an essential role in regulating malignant progression of tumour cells by inhibiting translation or stability of messenger RNA. However, the expression pattern and regulatory mechanism of miR-27-3p in osteosarcoma remains unclear. METHODS: We examined the expression of miR-27-3p in 5 osteosarcoma cell lines compared with that in 2 normal osteocyte cell lines. Osteosarcoma cells U-2OS and MG-63 were transduced to up-regulate or down-regulate the expression of miR-27-3p...
February 26, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
A Yajima, K Tsuchiya, L F Bonewald, M Inaba, Y Tominaga, T Tanizawa, A Ito, K Nitta
Evaluation of bone is of great importance in chronic kidney disease patients, as these patients are at an increased risk for fractures. We treated a hemodialysis patient suffering from hyperparathyroid bone disease with cinacalcet hydrochloride and concurrent administration of maxacalcitol and alfacalcidol for a year. Hyperparathyroid bone disease is characterized by cortical thinning, increased cortical porosity, reduced trabecular bone volume, and increased hypomineralized matrix volume, and there is little information to date about the effects of treatment with cinacalcet hydrochloride on the bone fragility in patients with hyperparathyroid bone disease...
February 28, 2018: Osteoporosis International
Jason A Bleedorn, Troy A Hornberger, Craig A Goodman, Zhengling Hao, Susannah J Sample, Ermias Amene, Mark D Markel, Mary Behan, Peter Muir
Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and mammalian target of rapamycin (mTOR)...
2018: PloS One
Divya Chaudhary, Raj Narayan Trivedi, Ashima Kathuria, Rekha Khandia, Tapas Kumar Goswami, Ashok Kumar Munjal
BACKGROUND: Mesenchymal stem cells (MSCs) are self-renewing, multipotent progenitor cells with multilineage potential to differentiate into all cell types of mesodermal origin, such as adipocytes, osteocytes and chondrocytes. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. OBJECTIVE: Besides the differentiation potential of MSCs, these also regulate the immune response in numerous ailments. The present review expeditesthe immunomodulating prospective of MSCs...
February 26, 2018: Recent Patents on Inflammation & Allergy Drug Discovery
Vivian Wu, René F M van Oers, Engelbert A J M Schulten, Marco N Helder, Rommel G Bacabac, Jenneke Klein-Nulend
Bone mass is important for dental implant success and is regulated by mechanoresponsive osteocytes. We aimed to investigate the relationship between the levels and orientation of tensile strain and morphology and orientation of osteocytes at different dental implant positions in the maxillary bone. Bone biopsies were retrieved from eight patients who underwent maxillary sinus-floor elevation with β-tricalcium phosphate prior to implant placement. Gap versus free-ending locations were compared using 1) a three-dimensional finite-element model of the maxilla to predict the tensile strain magnitude and direction and 2) histology and histomorphometric analyses...
February 26, 2018: International Journal of Oral Science
Takafumi Tajima, Kunitaka Menuki, Kayoko Furukawa Okuma, Manabu Tsukamoto, Hokuto Fukuda, Yasuaki Okada, Kenji Kosugi, Yoshiaki Yamanaka, Soshi Uchida, Akinori Sakai
Aldehyde dehydrogenase 2 (ALDH2) is the enzyme that degrades and detoxifies the acetaldehyde produced by alcohol metabolism. In our previous study, we found that compared with wild-type mice (WT), climbing exercises did not increase trabecular bone mass in Aldh2 knockout mice (KO). The purpose of this study was to clarify the effect of the Aldh2 gene on cortical bone structure and on the dynamics of skeletal unloading. Eight-week-old male KO and WT were divided into ground control (GC) or tail suspension (TS) groups for one week (i...
February 23, 2018: Bone
Jun Yin, Leixiang Han, Wei Cong
BACKGROUND: Long term use of glucocorticoids is one of the most common causes of secondary osteoporosis. Osteocyte, the most abundant cell type in bone, coordinates the function of osteoblast and osteoclast. This study evaluates the protective effect of alpinumisoflavone (AIF), a naturally occurring flavonoid compound, on dexamethasone (Dex)-induced apoptosis of osteocytes. METHODS: MLO-Y4 cell was used as a cell model. The effect of AIF on the cell viability was assessed by MTT assay...
November 4, 2017: Pharmacological Reports: PR
Mary F Barbe, Vicky S Massicotte, Soroush Assari, Alexandra M Monroy, Nagat Frara, Michele Y Harris, Mamta Amin, Tamara King, Geneva E Cruz, Steve N Popoff
We have an operant rat model of upper extremity reaching and grasping in which we examined the impact of performing a high force high repetition (High-ForceHR) versus a low force low repetition (Low-ForceHR) task for 18 weeks on the radius and ulna, compared to age-matched controls. High-ForceHR rats performed at 4 reaches/min and 50% of their maximum voluntary pulling force for 2 h/day, 3 days/week. Low-ForceHR rats performed at 6% maximum voluntary pulling force. High-ForceHR rats showed decreased trabecular bone volume in the distal metaphyseal radius, decreased anabolic indices in this same bone region (e...
February 21, 2018: Bone
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