A5101613537- Bone Metabolism and Diseases
- Bone health and treatments
- Bone health and osteoporosis research
- Metal complexes synthesis and properties
- Microtubule and mitosis dynamics
- Trace Elements in Health
- Erythrocyte Function and Pathophysiology
- Metal-Organic Frameworks: Synthesis and Applications
- Biomarkers in Disease Mechanisms
- Crystal structures of chemical compounds
- Cellular transport and secretion
- Antimicrobial Resistance in Staphylococcus
- Crystallization and Solubility Studies
- Cellular Mechanics and Interactions
- X-ray Diffraction in Crystallography
- Orthopedic Infections and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Bioactive Compounds and Antitumor Agents
- Biochemical and Molecular Research
- Bone and Dental Protein Studies
- NF-κB Signaling Pathways
- Medicinal Plant Studies
- Fibroblast Growth Factor Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Alkaline Phosphatase Research Studies
The University of Western Australia
2011-2023
International Medical University
2016-2021
Harvard University
2018-2019
University of Strathclyde
2018
Max Planck Society
2009
Max Planck Institute for Biophysical Chemistry
2009
Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that thought to undergo apoptosis once resorption is complete. Here, intravital imaging, we reveal RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted osteomorph accumulation. Single-cell RNA sequencing showed osteomorphs transcriptionally distinct...
Osteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result bacterial infection and severely perturbs structure. OM is predominantly caused by Staphylococcus aureus, even with proper treatment, has high rate recurrence chronicity. While S. aureus been shown to infect osteoblasts, it remains unclear whether osteoclasts (OCs) are also target intracellular infection. Here, we demonstrate the ability intracellularly divide within OCs. OCs were differentiated from...
(Cell 184, 1330–1347.e1–e13; March 4, 2021) As a result of an author oversight in the originally published version this article, name author, Alexander Corr, did not appear list. This error has now been corrected article online, and contributions have updated accordingly to reflect Corr’s scRNA-seq analysis. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorptionMcDonald et al.CellFebruary 25, 2021In BriefTracking osteoclasts cycles fission fusion reveals...
The parathyroid hormone 1 receptor (PTHR) is central to the process of bone formation and remodeling. PTHR signaling requires internalization into endosomes, which then terminated by recycling or degradation. Here we show that sorting nexin 27 (SNX27) functions as an adaptor couples retromer trafficking complex. SNX27 binds directly C-terminal PDZ-binding motif PTHR, wiring it for endosomal sorting. structure bound reveals a high-affinity interface involving conserved electrostatic...
ABSTRACT Osteal macrophages (osteomacs) support osteoblast function and promote bone anabolism, but their contribution to osteoporosis has not been explored. Although mouse ovariectomy (OVX) models have repeatedly used, variation in strain, experimental design assessment modalities contributed no single model being confirmed as comprehensively replicating the full gamut of pathological manifestations. We validated an OVX adult C3H/HeJ mice demonstrated that it presents with human...
Abstract Osteoclasts are giant bone-digesting cells that harbor specialized lysosome-related organelles termed secretory lysosomes (SLs). SLs store cathepsin K and serve as a membrane precursor to the ruffled border, osteoclast’s ‘resorptive apparatus’. Yet, molecular composition spatiotemporal organization of remains incompletely understood. Here, using organelle-resolution proteomics, we identify member a2 solute carrier 37 family (Slc37a2) SL sugar transporter. We demonstrate in mice...
Significance Cortical bone homeostasis combines periosteal formation and endocortical remodeling. Flaws in these processes lead to altered cortical mass. Yet, little is known about the regulatory specificities of vs. surfaces, both critical determining thickness. We have shown that Pyle’s disease due loss-of-function mutations Wnt antagonist SFRP4 its deletion mice causes skeletal deformities closely mimicking those seen disease: thinning. Here, we further elucidate mechanism by which...
Microtubule organization and lysosomal secretion are both critical for the activation function of osteoclasts, highly specialized polykaryons that responsible bone resorption skeletal homeostasis. Here, we have identified a novel interaction between microtubule regulator LIS1 Plekhm1, lysosome-associated protein implicated in osteoclast secretion. Decreasing expression by shRNA dramatically attenuated formation function, as shown decreased number mature osteoclasts differentiated from marrow...
ABSTRACT Aseptic loosening and periprosthetic infection leading to inflammatory osteolysis is a major complication associated with total joint arthroplasty (TJA). The liberation of bacterial products and/or implant-derived wear particles activates immune cells that produce pro-osteoclastogenic cytokines enhance osteoclast recruitment activity, bone destruction osteolysis. Therefore, agents prevent the response attenuate excessive (OC) formation resorption offer therapeutic potential by...
Background: Clinacanthus nutans (C.nutans) is a plant consumed as cancer treatment in tropical Asia. Despite the availability of numerous anecdotal reports, evaluation active anticancer effects has remained elusive. Therefore we here examined antiproliferative, reactive oxygen species (ROS)-inducing and apoptosis mechanisms whole extracts different cell lines. Methods: Antiproliferative actions five solvent (hexane, chloroform, ethyl acetate, methanol water) C.nutans were tested on non-small...
Even though an increasing number of anticancer treatments have been discovered, the mortality rates colorectal cancer (CRC) still high in past few years. It has discovered that melatonin pro-apoptotic properties and counteracts inflammation, proliferation, angiogenesis, cell invasion, migration. In previous studies, shown to effect multiple tumors, including CRC, but underlying mechanisms action on CRC not fully explored. Thus, this study, we investigated role autophagy pathways cells...
Vesicular transport along microtubules must be strictly regulated to sustain the unique structural and functional polarization of bone-resorbing osteoclasts. However, molecular mechanisms bridging these vesicle-microtubule interactions remain largely obscure. Rab3D, a member Rab3 subfamily (Rab3A/B/C/D) small exocytotic GTPases, represents core component osteoclastic vesicle machinery. Here, we identify new Rab3D-interacting partner, Tctex-1, light chain cytoplasmic dynein microtubule motor...
Bioceramics for regenerative medicine applications should have the ability to promote adhesion, proliferation and differentiation of osteoblast osteoclast cells. Osteogenic properties material are essential rapid bone regeneration new formation. The aim this study was develop a silicate-based ceramic, gehlenite (GLN, Ca2Al2SiO7), characterise its physiochemical, biocompatibility osteogenic properties. A pure GLN powder synthesised by facile reactive sintering method compacted disc-shaped...
Three ternary copper(II) complexes, [Cu(phen)(L-phe)Cl]·2H2O, [Cu(phen)(L-leu)Cl]·4½H2O, and [Cu(phen)(L-tyr)Cl]·3H2O, four binary [Cu(phen)Cl2], Cu(L-phe)2·½H2O, Cu(L-leu)2·½H2O, Cu(L-tyr)2·H2O (where phen = 110-phenanthroline, L-phe L-phenylalanine, L-tyr L-tyrosine, L-leu L-leucine Cl- chloride), were synthesized characterized by elemental analysis, spectroscopic techniques (FTIR, UV–visible, fluorescence spectroscopy), magnetic susceptibility, molar conductivity, lipophilicity...
Abstract Osteoclastic bone resorption requires strict interplay between acidified carrier vesicles, motor proteins, and the underlying cytoskeleton in order to sustain specialized structural functional polarization of ruffled border. Cytoplasmic dynein, a large processive mechanochemical comprising heavy, intermediate, light chains coupled dynactin cofactor complex, powers unilateral motility diverse cargos microtubule minus-ends. We have recently shown that regulators dynein complex...
ABSTRACT Atypical femoral fractures (AFFs) are a rare but potentially devastating event, often not always linked to bisphosphonate (BP) therapy. The pathogenic mechanisms underlying AFFs remain obscure, and there no tests available that might assist in identifying those at high risk of AFF. We previously used exome sequencing explore the genetic background three sisters with additional unrelated AFF cases, all treated BPs. detected 37 mutations (in 34 genes) shared by sisters. Notably, we...
Bone remodeling is intrinsically regulated by cell signaling molecules. The Protein Kinase C (PKC) family of serine/threonine kinases involved in multiple pathways including proliferation, differentiation, apoptosis and osteoclast biology. However, the precise involvement individual PKC isoforms regulation formation bone homeostasis remains unclear. Here, we identify PKC-δ as major isoform expressed among all PKCs osteoclasts; classical (−α, −β −γ), novel (−δ, −ε, −η −θ) atypical (−ι/λ −ζ)....
The complexes induced apoptosis <italic>via</italic> ROS production, drop in mitochondrial membrane potential and epigenetic changes.