Journals Journal of Bone and Mineral Re...

Journal of Bone and Mineral Research
Hui Dong, Ronghan Liu, Ke Zou, Zhengxin Jin, Jianning Kang, Ying Zhang, Xiaodi Zhang, Zhengfang Sun, Guilian Yu, Nana Huang, Morgan Bretches, Shang-You Yang, Bin Ning
Osteoporosis is a common bone disease caused by an imbalance of bone resorption and formation that results in a loss of total bone density. SMAD2/3 signal transduction is known to plays a crucial role in osteogenic differentiation through transforming growth factor-beta (TGF-β). By screening a library of small-molecule compounds, the current study identifies Higenamine (HG) as an active osteogenic agent that may be a potential therapeutic candidate for osteoporosis. In vitro data demonstrated that HG effectively induced expressions of osteogenic markers in mouse bone marrow stromal cell (BMSCs) and pre-osteoblastic cell cultures...
March 12, 2023: Journal of Bone and Mineral Research
Dominyka Batkovskyte, Fiona McKenzie, Fulya Taylan, Pelin Ozlem Simsek-Kiper, Sarah M Nikkel, Hirofumi Ohashi, Roger E Stevenson, Thuong Ha, Denise P Cavalcanti, Hiroyuki Miyahara, Steven A Skinner, Miguel A Aguirre, Zühal Akçören, Gulen Eda Utine, Tillie Chiu, Kenji Shimizu, Anna Hammarsjö, Koray Boduroglu, Hannah W Moore, Raymond J Louie, Peer Arts, Allie N Merrihew, Milena Babic, Matilda R Jackson, Nikos Papadogiannakis, Anna Lindstrand, Ann Nordgren, Christopher P Barnett, Hamish S Scott, Andrei S Chagin, Gen Nishimura, Giedre Grigelioniene
Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356) is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly...
March 10, 2023: Journal of Bone and Mineral Research
Roy B Choi, April M Hoggatt, Daniel J Horan, Emily Z Rogers, Gabriela G Loots, Alexander G Robling
The development of Wnt-based osteoanabolic agents have progressed rapidly in recent years, given the potent effects of Wnt modulation on bone homeostasis. Simultaneous pharmacologic inhibition of the Wnt antagonists sclerostin and Dkk1 can be optimized to create potentiated effects in the cancellous bone compartment. We looked for other candidates that might be co-inhibited along with sclerostin to potentiate the effects in the cortical compartment. Sostdc1 (Wise), like sclerostin and Dkk1, also binds and inhibits Lrp5/6 co-receptors to impair canonical Wnt signaling, but Sostdc1 has greater effects in the cortical bone...
March 9, 2023: Journal of Bone and Mineral Research
Melanie Haffner-Luntzer, Deniz Ragipoglu, Mubashir Ahmad, Astrid Schoppa, Lena Steppe, Verena Fischer, Julia Luther, Timur Yorgan, Ernesto Bockamp, Michael Amling, Thorsten Schinke, Anita Ignatius
Despite considerable improvement in fracture care, 5-10% of all fractures still heal poorly or result in non-union formation. Therefore, there is the urgent need to identify new molecules that can be used to improve bone fracture healing. One activator of the Wnt-signaling cascade, Wnt1, has recently gained attention for its intense osteoanabolic effect on the intact skeleton. The aim of the present study was to investigate whether Wnt1 might be a promising molecule to accelerate fracture healing both in skeletally healthy and osteoporotic mice that display a diminished healing capacity...
March 9, 2023: Journal of Bone and Mineral Research
Benoit Gobron, Malory Couchot, Nigel Irwin, Erick Legrand, Béatrice Bouvard, Guillaume Mabilleau
Due to ageing of the population, bone frailty is dramatically increasing worldwide. Although some therapeutic options exist, they do not fully protect or prevent against the occurrence of new fractures. All current drugs approved for the treatment of bone fragility target bone mass. However, bone resistance to fracture is not solely due to bone mass but relies also on bone extracellular matrix (ECM) material properties, i.e. the quality of the bone matrix component. Here, we introduce the first-in-class unimolecular dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide -2 (GIP/GLP-2) analogues, GL-0001, that activates simultaneously the glucose-dependent insulinotropic polypeptide receptor (GIPr) and the glucagon-like peptide-2 receptor (GLP-2r)...
February 27, 2023: Journal of Bone and Mineral Research
Jordan Tzvetkov, Louise A Stephen, Scott Dillon, Jose Luis Milan, Anke J Roelofs, Cosimo De Bari, Colin Farquharson, Tony Larson, Paul Genever
Lipids play a crucial role in signalling and metabolism, regulating the development and maintenance of the skeleton. Membrane lipids have been hypothesised to act as intermediates upstream of orphan phosphatase 1 (PHOSPHO1), a major contributor to phosphate generation required for bone mineralisation. Here, we spatially resolve the lipid atlas of the healthy mouse knee and demonstrate the effects of PHOSPHO1 ablation on the growth plate lipidome. Lipids spanning 17 subclasses were mapped across the knee joints of healthy juvenile and adult mice using matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-IMS), with annotation supported by shotgun lipidomics...
February 23, 2023: Journal of Bone and Mineral Research
Neelam Hassan, Celia L Gregson, Haotian Tang, Marc van der Kamp, Paul Leo, Aideen M McInerney-Leo, Jie Zheng, Maria Luisa Brandi, Jonathan Cy Tang, William Fraser, Michael D Stone, Elin Grundberg, Matthew A Brown, Emma L Duncan, Jonathan H Tobias
Anabolic treatment options for osteoporosis remain limited. One approach to discovering novel anabolic drug targets is to identify genetic causes of extreme high bone mass (HBM). We investigated a pedigree with unexplained HBM within the UK HBM study, a national cohort of probands with HBM and their relatives. Whole exome sequencing (WES) in a family with HBM identified a rare heterozygous missense variant (NM_004482.4:c.1657C>T, p.Arg553Trp) in GALNT3, segregating appropriately. Interrogation of data from the UK HBM study and the Anglo-Australasian Osteoporosis Genetics Consortium (AOGC) revealed an unrelated individual with HBM with another rare heterozygous variant (NM_004482...
February 23, 2023: Journal of Bone and Mineral Research
(no author information available yet)
No abstract text is available yet for this article.
February 21, 2023: Journal of Bone and Mineral Research
Carrie Ye, Suzanne N Morin, Lisa M Lix, Eugene V McCloskey, Helena Johansson, Nicholas C Harvey, John A Kanis, William D Leslie
FRAX® was created to predict major osteoporotic fractures (MOF) and hip fractures in the general population. Whether FRAX accurately predicts fractures in men with prostate cancer is unknown. Our objective was to assess the performance of FRAX for predicting incident fractures in men with prostate cancer. Men from the Manitoba Bone Mineral Density (BMD) Registry (1996-2018) with prostate cancer diagnoses in the 3 years prior to dual-energy X-ray absorptiometry (DXA) were identified. FRAX scores with and without BMD were calculated...
February 20, 2023: Journal of Bone and Mineral Research
Douglas Ralph, Michael Levine, José Luis Millán, Jouni Uitto, Qiaoli Li
Ectopic calcification is characterized by inappropriate deposition of calcium mineral in non-skeletal connective tissues and can cause significant morbidity and mortality, particularly when it affects the cardiovascular system. Identification of the metabolic and genetic determinants of ectopic calcification could help distinguish individuals at greatest risk of developing these pathological calcifications and could guide development of medical interventions. Inorganic pyrophosphate (PPi ) has long been recognized as the most potent endogenous inhibitor of biomineralization...
February 20, 2023: Journal of Bone and Mineral Research
Tingyi Cao, Jiaxuan Zhao, Xiumei Hong, Guoying Wang, Colleen Pearson, William G Adams, Frank B Hu, Xiaobin Wang, Liming Liang
Although the maternal intrauterine metabolic environment has been recognized to have a profound impact on fetal growth and development with lifelong health implications, to our knowledge, there have been few large-scale birth cohort studies linking the cord metabolome (reflecting both the maternal and fetal metabolic state) with postnatal height measurements across the pediatric age range. Using data from the Boston Birth Cohort, an ongoing prospective birth cohort, this study investigated the association of cord plasma metabolites with children's height from birth to adolescence...
February 20, 2023: Journal of Bone and Mineral Research
Richard Prince, Benjamin Khoo, Joshua Lewis
We examine the hypothesis that DXA structural variables measured at the femoral neck and trochanter cross sections will improve prediction of fractures at these sites in addition to areal BMD (aBMD). We present an analysis of the internal distribution of bone at the site of these fractures using baseline hip DXA measurement of 1,151 participants, mean age (SD) 75 (3), in the 15-year Perth Longitudinal Study of Aging in Women. Structural differences at the femoral neck (FN) and trochanter (TR) cross sections were compared in 69 participants who went on to sustain femoral neck fracture (FNF) and 59 participants who went on to sustain trochanter fracture (TRF), on average ten years later, to those who did not fracture...
February 16, 2023: Journal of Bone and Mineral Research
Jocelyn Tan, Carrie-Anne Ng, Nicolas Hart, Timo Rantalainen, Marc Sim, David Scott, Kun Zhu, Beth Hands, Paola Chivers
Although suboptimal bone health has been reported in children and adolescents with low motor competence (LMC), it is not known whether such deficits are present at the time of peak bone mass. We examined the impact of LMC on bone mineral density (BMD) in 1043 participants (484 females) from the Raine Cohort Study. Participants had motor competence assessed using the McCarron Assessment of Neuromuscular Development at 10, 14, and 17 years, and a whole body dual-energy X-ray absorptiometry scan at 20 years...
February 16, 2023: Journal of Bone and Mineral Research
Rubens Sautchuk, Chen Yu, Matthew McArthur, Christine Massie, Paul S Brookes, George A Porter, Hani Awad, Roman A Eliseev
The mitochondrial permeability transition pore (MPTP) and its positive regulator, cyclophilin D (CypD), play important pathophysiological roles in aging. In bone tissue, higher CypD expression and pore activity are found in aging, however a causal relationship between CypD/MPTP and bone degeneration needs to be established. We previously reported that CypD expression and MPTP activity are downregulated during osteoblast (OB) differentiation and that manipulations in CypD expression affect OB differentiation and function...
February 13, 2023: Journal of Bone and Mineral Research
Luisa F Valenzuela Riveros, Jin Long, Laura K Bachrach, Mary B Leonard, Kyla Kent
Trabecular bone score (TBS) derived from secondary analysis of lumbar spine DXA scans improves fracture prediction independent of BMD in adults. The utility of TBS to assess fracture risk in younger patients has not been established because pediatric norms have been lacking. Robust TBS reference data from the Bone Mineral Density in Childhood Study (BMDCS) have been published. TBS values for the BMDCS study were derived using an algorithm that accounts for tissue thickness (TBSTH ) rather than the commercially-available algorithm that adjusts for BMI (TBSBMI )...
February 13, 2023: Journal of Bone and Mineral Research
John P Bilezikian, Merav Fraenkel, Liana Tripto-Shkolnik, Rene Rizzoli, Ethel Siris
No abstract text is available yet for this article.
February 11, 2023: Journal of Bone and Mineral Research
Christopher J Hernandez
No abstract text is available yet for this article.
February 8, 2023: Journal of Bone and Mineral Research
Tingting Yu, Guoqiang Li, Chen Wang, Niu Li, Ruen Yao, Jian Wang
Multiple synostoses syndromes (SYNS) are a group of rare genetic bone disorders characterized by multiple joint fusions. We previously reported an SYNS4-causing GDF6 c.1330T>A (p.Tyr444Asn) mutation, which reduced Noggin-induced GDF6 inhibition and enhanced SMAD1/5/8 signaling. However, the mechanisms by which GDF6 gain-of-function mutation alters joint formation and the comprehensive molecular portraits of SYNS4 remain unclear. Herein, we introduced the p.Tyr443Asn (orthologous to the human GDF6 p.Tyr444Asn) mutation into the mouse Gdf6 locus and performed extensive phenotype analysis, joint development investigation, and transcriptome profiling of Gdf6 p...
February 6, 2023: Journal of Bone and Mineral Research
Yixuan Cao, Lulu Li, Xiuzhi Ren, Bin Mao, Yujiao Yang, Huan Mi, Yun Guan, Shan Li, Siji Zhou, Xin Guan, Tao Yang, Xiuli Zhao
Osteogenesis imperfecta (OI) is a hereditary skeletal disorder that is mainly caused by variants in COL1A1/2. So far, no specific treatment has been developed to correct its underlying etiology. We aimed to gain a better understanding of the pathological mechanisms of OI and develop gene editing techniques to correct OI-causing variants. A de novel cis-double-variant c.[175C>T;187T>A] in COL1A1 was identified from a 5-year-old OI patient by whole exome sequencing. Three peptide nucleic acids (PNAs) were designed and then transfected patient-derived fibroblasts...
February 3, 2023: Journal of Bone and Mineral Research
Tafadzwa Madanhire, Julia H Goedecke, Kate A Ward, Nicole Jaff, Nigel J Crowther, Shane Norris, Rashida A Ferrand, Andrea M Rehman, Lisa K Micklesfield, Celia L Gregson
An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up...
February 1, 2023: Journal of Bone and Mineral Research
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