Louise A. Stephen

TNAP and PHOSPHO1 Function Synergistically to Afford Critical Control Over the Mineralization of the Postnatal Murine Skeleton

Lucie E. Bourne, Aikta Sharma, Scott Dillon, Jacob A. C. Keen et autres

ABSTRACT Biomineralization is essential for skeletal integrity, yet the synergistic roles of tissue non‐specific alkaline phosphatase (TNAP) and PHOSPHO1 in postnatal bone remain unclear. We generated a novel murine model with Prx1 ‐driven deletion of Alpl ( Alpl Prx1/Prx1 ) on a …

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Bispecific antibody against sclerostin and DKK1 improves bone health and reduces bone marrow adipose tissue accumulation in experimental chronic kidney disease

Worachet Promruk, Soher Nagi Jayash, Chartinun Chutoe, Hua Zhu Ke et autres

Chronic kidney disease (CKD) leads to bone loss and bone marrow adipose tissue (BMAT) accumulation. Sclerostin and dickkopf-1 (DKK1) are two inhibitors of Wnt signalling, which suppress bone formation, promote bone marrow adipogenesis, and are elevated in CKD. However, therapies targeting sclerostin …

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Prpf8 N1531S homozygous mutant mouse embryos have multiple defects in cardiac development and show aberrant splicing of the cardiac transcription factor Tead1

Wasay Mohiuddin Shaikh Qureshi, Haoxiang Zhou, Abigail Bennington, Nouf J. Althali et autres

Abstract Mutations in the spliceosomal gene PRPF8 are associated with a range of human diseases. Studies in mouse and zebrafish suggest that Prpf8 also has a developmental function. Here, using a Prpf8 mutant mouse line isolated from a chemical induced mutagenesis screen, …

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TNAP and PHOSPHO1 function synergistically to afford critical control over the mineralisation of the postnatal murine skeleton

Lucie E. Bourne, Aikta Sharma, Scott Dillon, Jacob A. C. Keen et autres

Abstract Biomineralisation is essential for skeletal integrity, yet the synergistic roles of tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 in postnatal bone mineralisation remain poorly defined. To decipher this, we generated a novel murine model in which Alpl was deleted in Prx1 …

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Maintenance of bone health by osteoblasts in the absence of osteocytes: comparative analysis of gene expression in medaka and zebrafish vertebrae

Soher Nagi Jayash, DR Dunbar, S Guizard, J Furniss et autres

Proteomic characterisation of matrix vesicles from primary osteoblasts indicates a mixed population with both exosomal and ectosomal routes of biogenesis

Scott Dillon, Charlotte Clews, Dominic Kurian, Fabio Nudelman et autres

Abstract Matrix Vesicles are a crucial step in producing a mineralised, healthy skeleton. Released from chondrocytes and osteoblasts, they concentrate calcium and phosphate to establish the deposition of hydroxyapatite around and within the collagen fibrils of the extracellular matrix, becoming embedded in …

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Bone marrow adipose tissue expansion and bone loss in experimental chronic kidney disease is independent of altered bone marrow stromal cell lineage determination

Worachet Promruk, William Peter Cawthorn, Lucie E. Bourne, Soher Nagi Jayash et autres

Introduction: Chronic kidney disease-mineral bone disorder is the irreversible loss of kidney function leading to altered mineral homeostasis and bone loss, commonly referred to as renal osteodystrophy. Bone marrow adipose tissue (BMAT) accumulates in clinical CKD and animal models of this disease, …

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Nanofiber‐Coated CF/PEEK Composite: Boosting Osteogenesis for Enhanced Bone Grafting

Dan‐Lei Yang, Louise A. Stephen, Junaid Ahmad Qayyum, Dongmin Yang et autres

Front Cover: This illustration depicts the integration of 3D printing and electrospinning to fabricate nanofiber-coated scaffolds. Incorporating hydroxyapatite-loaded nanofibers significantly boosts osteogenesis, hydrophilicity, and cell compatibility. This multifunctional surface engineering strategy offers a powerful route toward next-generation bone graft substitutes with tailored …

Taking a closer look at matrix vesicle biogenesis

Charlotte Clews, Scott Dillon, Fabio Nudelman, Colin Farquharson et autres

Matrix vesicles (MVs) are crucial components in the development of a healthy mineralized skeleton. They are also the key elements leading to the pathological calcification of vasculature; however, we know surprisingly little about them. First characterized over 55 yr ago, MVs are …

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The RNA splicing factor PRPF8 is required for left-right organiser cilia differentiation and determination of cardiac left-right asymmetry via regulation of Arl13b splicing

Michael Boylan, Dale W. Maxwell, Wasay Mohiuddin Shaikh Qureshi, Charlie F Rowlands et autres

Cilia function in the left-right organizer (LRO) is critical for determining internal organ asymmetry in vertebrates. To further understand the genetics of left-right asymmetry, we isolated a mouse mutant with laterality defects, l11Jus27, from a random mutagenesis screen. l11Jus27 mutants carry a …

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Mitochondrial dysfunction and mitophagy blockade contribute to renal osteodystrophy in chronic kidney disease-mineral bone disorder

Shun‐Neng Hsu, Louise A. Stephen, Kanchan Phadwal, Scott Dillon et autres

Chronic kidney disease-mineral and bone disorder (CKD-MBD) presents with extra-skeletal calcification and renal osteodystrophy (ROD). However, the pathophysiology of ROD remains unclear. Here we examine the hypothesis that stalled mitophagy within osteocytes of CKD-MBD mouse models contributes to bone loss. RNA-seq analysis …

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Nanofiber‐Coated CF/PEEK Composite: Boosting Osteogenesis for Enhanced Bone Grafting

Dan‐Lei Yang, Louise A. Stephen, Junaid Ahmad Qayyum, Dongmin Yang et autres

Abstract This study presents the fabrication of carbon‐fiber‐reinforced polyetheretherketone (CF/PEEK) by 3D printing, which is subsequently coated with elastic nanofibers by electrospinning. CF/PEEK is an FDA‐approved implantable material possessing excellent mechanical properties similar to those of human cortical bone. As such, it …

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