Withdrawal of parathyroid hormone after prolonged administration leads to adipogenic differentiation of mesenchymal precursors in vivo
Intermittent PTH-like drugs are the only approved so-called anabolic agent that increases bone mass in both mice and humans. It is well documented that PTH targets mature cells of the osteoblast lineage, with only indirect evidence of its actions on early cells of the osteoblast lineage. Using a triple transgenic mouse model that allowed labeling of very early cells of the osteoblast lineage, we traced the progeny of these into osteoblast lineage in adult mice. These early cells expressed PTH1R and multiplied when PTH (1 –34) was administered daily. (Source: Bone)
Source: Bone - May 22, 2018 Category: Orthopaedics Authors: Deepak H. Balani, Henry M. Kronenberg Tags: Full Length Article Source Type: research
Preservation of type H vessels and osteoblasts by enhanced preosteoclast platelet-derived growth factor type BB attenuates glucocorticoid-induced osteoporosis in growing mice
Survival of chronic diseases in childhood is often achieved utilizing glucocorticoids, but comes with significant side effects, including glucocorticoid-induced osteoporosis (GIO). Knowledge of the mechanism of GIO is limited to the adult skeleton. We explored the effect of genetic loss and inhibition of cathepsin K (Ctsk) as a potential treatment target in a young GIO mouse model as genetic loss of cathepsin K results in a mild form of osteopetrosis secondary to impaired osteoclast bone resorption with maintenance of bone formation. (Source: Bone)
Source: Bone - May 22, 2018 Category: Orthopaedics Authors: Ping Yang, Shan Lv, Yan Wang, Yi Peng, Zixing Ye, Zhuying Xia, Guoxian Ding, Xu Cao, Janet L. Crane Tags: Full Length Article Source Type: research
LP533401 restores bone health in 5/6 nephrectomized rats by a decrease of gut-derived serotonin and regulation of serum phosphate through the inhibition of phosphate co-transporters expression in the kidneys
LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia. Sixteen weeks after 5/6 nephrectomy, rats were randomized into untreated (CKD), treated with vehicle (VEH) and LP533401 at a dose of 30 or 100 mg/kg daily for 8 weeks. (Source: Bone)
Source: Bone - May 21, 2018 Category: Orthopaedics Authors: Dariusz Pawlak, Beata Znorko, Bartlomiej Kalaska, Tomasz Domaniewski, Rados ław Zawadzki, Paweł Lipowicz, Michał Doroszko, Urszula Łebkowska, Piotr Grabowski, Krystyna Pawlak Tags: Full Length Article Source Type: research
A comparative study of quality of life, functional and bone outcomes in osteogenesis imperfecta with bisphosphonate therapy initiated in childhood or adulthood
This study describes functional outcomes of a cohort of adults with OI, stratified according to severity and treated with intravenous bisphosphonates as children. (Source: Bone)
Source: Bone - May 19, 2018 Category: Orthopaedics Authors: Andrew G. Feehan, Margaret R. Zacharin, Angelina S. Lim, Peter J. Simm Tags: Full Length Article Source Type: research
Defining osteoblast and adipocyte lineages in the bone marrow
Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood. (Source: Bone)
Source: Bone - May 18, 2018 Category: Orthopaedics Authors: J.L. Pierce, D.L. Begun, J.J. Westendorf, M.E. McGee-Lawrence Tags: Full Length Article Source Type: research
Global deletion of tetraspanin CD82 attenuates bone growth and enhances bone marrow adipogenesis
CD82 is a widely expressed member of the tetraspanin family of transmembrane proteins known to control cell signaling, adhesion, and migration. Tetraspanin CD82 is induced over 9-fold during osteoclast differentiation in vitro; however, its role in bone homeostasis is unknown. A globally deleted CD82 mouse model was used to assess the bone phenotype. Based on microCT and 4-point bending tests, CD82-deficient bones are smaller in diameter and weaker, but display no changes in bone density. Histomorphometry shows a decrease in size, erosion perimeter, and number of osteoclasts in situ, with a corresponding increase in trabec...
Source: Bone - May 18, 2018 Category: Orthopaedics Authors: Alexis Bergsma, Sourik S. Ganguly, Daniel Dick, Bart O. Williams, Cindy K. Miranti Tags: Full Length Article Source Type: research
Sex differences in the spatial distribution of bone in relation to incident hip fracture: Findings from the AGES-Reykjavik study
In this case-cohort study, we used data-driven computational anatomy approaches to assess within and between sex spatial differences in proximal femoral bone characteristics in relation to incident hip fracture. One hundred male and 234 female incident hip fracture cases, and 1047 randomly selected noncase subcohort participants (562 female) were chosen from the population-based AGES-Reykjavik study (mean age of 77 years). The baseline –i.e. before hip fracture– hip quantitative computed tomography scans of these subjects were analyzed using voxel-based morphometry, tensor-based morphometry, and surface-based statis...
Source: Bone - May 17, 2018 Category: Orthopaedics Authors: Elisa A. Marques, Julio Carballido-Gamio, Vilmundur Gudnason, Gunnar Sigurdsson, Sigurdur Sigurdsson, Thor Aspelund, Kristin Siggeirsdottir, Lenore Launer, Gudny Eiriksdottir, Thomas Lang, Tamara B. Harris Tags: Full Length Article Source Type: research
The hematopoietic stem cell niche: What's so special about bone?
Hematopoietic stem cells (HSCs) require a supportive microenvironment to regulate their function and produce sufficient hematopoietic cells over the lifetime of an individual. With the exception of fish, all vertebrates, including mammals, maintain HSCs in a complex niche within the bone marrow. Several bone specific cellular populations have been implicated as components of the HSC niche and are part of a complex network that regulates HSC functions. However, the full extent of interactions within the HSC niche, and the role of individual cell populations remain to be fully elucidated. (Source: Bone)
Source: Bone - May 17, 2018 Category: Orthopaedics Authors: Benjamin J. Frisch Tags: Review Article Source Type: research
Brain to bone: What is the contribution of the brain to skeletal homeostasis?
The brain, which governs most, if not all, physiological functions in the body, from the complexities of cognition, learning and memory, to the regulation of basal body temperature, heart rate and breathing, has long been known to affect skeletal health. In particular, the hypothalamus – located at the base of the brain in close proximity to the medial eminence, where the blood-brain-barrier is not as tight as in other regions of the brain but rather “leaky”, due to fenestrated capillaries – is exposed to a variety of circulating body cues, such as nutrients (glucose, fatt y acids, amino acids), and hormones (insul...
Source: Bone - May 17, 2018 Category: Orthopaedics Authors: Anna Idelevich, Roland Baron Tags: Review Article Source Type: research
The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis
Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types. Our synthesized r-irisin could promote proliferation and differentiation of osteoblasts as evidenced by enhanced expression of osteoblast-specific transcriptional f...
Source: Bone - May 15, 2018 Category: Orthopaedics Authors: Dingdong Zhang, ChuHyun Bae, Junghak Lee, Jiho Lee, Zeyu Jin, Myeongmo Kang, Young Suk Cho, Jeong-Han Kim, Weontae Lee, Sung-Kil Lim Tags: Full Length Article Source Type: research
Aortic vascular calcification is inversely associated with the trabecular bone score in patients receiving dialysis
Progressive chronic kidney disease (CKD) confers a marked increase in risk for vascular calcification, cardiovascular disease, fracture and mortality, with likely contributing factors including dysregulated bone metabolism and mineral homeostasis. In general population studies, increased vascular calcification is directly related to mortality and inversely related to bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). In patients with CKD, abnormalities in turnover, mineralization and bone volume, reduce the ability of DXA to predict fracture. (Source: Bone)
Source: Bone - May 15, 2018 Category: Orthopaedics Authors: Jasna Aleksova, Samantha Kurniawan, Mirna Vucak-Dzumhur, Peter Kerr, Peter R. Ebeling, Frances Milat, Grahame J. Elder Tags: Full Length Article Source Type: research
The anti-epileptic drugs valproate, carbamazepine and levetiracetam cause bone loss and modulate Wnt inhibitors in normal and ovariectomised rats
Secondary osteoporosis is the major concern associated with long term intake of antiepileptic drugs (AEDs). Women are the vulnerable targets owing to post-menopausal bone loss. In the present work, we evaluated the effect of 10 weeks of treatment with AED therapy (carbamazepine, CBZ, 75 mg/kg; sodium valproate, SVP, 300 mg/kg; levetiracetam, LTM, 150 mg/kg) on bone mineral density and microarchitecture at femoral epiphysis, lumbar vertebrae and proximal tibia of normal and ovariectomised Wistar rats. (Source: Bone)
Source: Bone - May 12, 2018 Category: Orthopaedics Authors: Bushra Parveen, Ambrish Kumar Tiwari, Moon Jain, Subhashis Pal, Naibedya Chattopadhyay, Manjari Tripathi, Divya Vohora Tags: Full Length Article Source Type: research
Integration of summary data from GWAS and eQTL studies identified novel causal BMD genes with functional predictions
Osteoporosis is a common global health problem characterized by low bone mineral density (BMD) and increased risk of fracture. Genome-wide association studies (GWAS) have identified>100 genetic loci associated with BMD. However, the functional genes responsible for most associations remain largely unknown. We conducted an innovative summary statistic data-based Mendelian randomization (SMR) analysis to identify novel causal genes associated with BMD and explored their potential functional significance. (Source: Bone)
Source: Bone - May 12, 2018 Category: Orthopaedics Authors: Xiang-He Meng, Xiang-Ding Chen, Jonathan Greenbaum, Qin Zeng, Sheng-Lan You, Hong-Mei Xiao, Li-Jun Tan, Hong-Wen Deng Tags: Full Length Article Source Type: research
Bone accrual in oligo-amenorrheic athletes, eumenorrheic athletes and non-athletes
Mechanical loading improves bone mineral density (BMD) and strength while decreasing fracture risk. Cross-sectional studies show that exercise advantage is lost in oligo-amenorrheic athletes (OA). Longitudinal studies examining the opposing effects of exercise and hypogonadism on bone are lacking in adolescents/young adults. (Source: Bone)
Source: Bone - May 11, 2018 Category: Orthopaedics Authors: Vibha Singhal, Karen Campoverde Reyes, Brooke Pfister, Kathryn Ackerman, Meghan Slattery, Katherine Cooper, Alexander Toth, Nupur Gupta, Mark Goldstein, Kamryn Eddy, Madhusmita Misra Tags: Full Length Article Source Type: research
Early TGF- β inhibition in mice reduces the incidence of breast cancer induced bone disease in a myeloid dependent manner
The tumor-cell microenvironment is recognized as a dynamic place where critical cell interactions occur and play an important role in altering tumorigenesis. While many studies have investigated the effects of cellular cross-talk within distinct tumor microenvironments, these interactions have yet to be fully examined in bone. It is well-established that many common cancers metastasize to bone, resulting in the development of tumor-induced bone disease (TIBD), a multi-facetted illness that is driven by complex cell interactions within the bone marrow. (Source: Bone)
Source: Bone - May 10, 2018 Category: Orthopaedics Authors: Denise Buenrostro, Kristin A. Kwakwa, Nicole E. Putnam, Alyssa R. Merkel, Joshua R. Johnson, James E. Cassat, Julie A. Sterling Tags: Full Length Article Source Type: research
