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Sexually dimorphic effects of prenatal alcohol exposure on the murine skeleton (2024)
Journal Article
Bourne, L., Jayash, S., Michels, L., Hopkinson, M., Guppy, F., Clarkin, C., …Staines, K. (2024). Sexually dimorphic effects of prenatal alcohol exposure on the murine skeleton. Biology of Sex Differences, 15(1), https://doi.org/10.1186/s13293-024-00626-y

Background Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies and increased bone fracture risk. However, the effects of PAE on the... Read More about Sexually dimorphic effects of prenatal alcohol exposure on the murine skeleton.

Autoimmunity to stromal-derived autoantigens in rheumatoid ectopic germinal centers exacerbates arthritis and affects clinical response (2024)
Journal Article
Corsiero, E., Caliste, M., Jagemann, L., Fossati-Jimack, L., Goldmann, K., Cubuk, C., …Bombardieri, M. (2024). Autoimmunity to stromal-derived autoantigens in rheumatoid ectopic germinal centers exacerbates arthritis and affects clinical response. Journal of Clinical Investigation, 134(12), https://doi.org/10.1172/JCI169754

Ectopic lymphoid structures (ELSs) in the rheumatoid synovial joints sustain autoreactivity against locally expressed autoantigens. We recently identified recombinant monoclonal antibodies (RA-rmAbs) derived from single, locally differentiated rheuma... Read More about Autoimmunity to stromal-derived autoantigens in rheumatoid ectopic germinal centers exacerbates arthritis and affects clinical response.

A new method for segmentation and analysis of bone callus in rodent fracture models using micro-CT (2022)
Journal Article
Hopkinson, M., Jones, G., Evans, L., Gohin, S., Magnusdottir, R., Salmon, P., …Pitsillides, A. (2022). A new method for segmentation and analysis of bone callus in rodent fracture models using micro-CT. Journal of Orthopaedic Research, https://doi.org/10.1002/jor.25507

Fracture burden has created a need to better understand bone repair processes under different pathophysiological states. Evaluation of structural and material properties of the mineralized callus, which is integral to restoring biomechanical stabilit... Read More about A new method for segmentation and analysis of bone callus in rodent fracture models using micro-CT.

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats (2022)
Journal Article
Tang, P., Jepson, R., Chang, Y., Geddes, R., Hopkinson, M., & Elliott, J. (2022). Risk factors and implications associated with renal mineralization in chronic kidney disease in cats. Journal of Veterinary Internal Medicine, https://doi.org/10.1111/jvim.16363

Background
Nephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored.

Objectives
Identify nephrocalcinosis risk factors and evaluate its influence on CKD prog... Read More about Risk factors and implications associated with renal mineralization in chronic kidney disease in cats.

Fracture-induced pain-like behaviours in a femoral fracture mouse model (2021)
Journal Article
Magnusdottir, R., Gohin, S., ter Heegde, F., Hopkinson, M., McNally, I., Fisher, A., …Chenu, C. (2021). Fracture-induced pain-like behaviours in a femoral fracture mouse model. Osteoporosis International, 32(11), 2347-2359. https://doi.org/10.1007/s00198-021-05991-7

This study is the first comprehensive characterisation of the pain phenotype after fracture using both evoked and naturalistic behaviours in adult male and ovariectomised female mice. It also shows that an anti-nerve growth factor (NGF) therapy could... Read More about Fracture-induced pain-like behaviours in a femoral fracture mouse model.

Bimodal Whole-Mount Imaging of Tendon Using Confocal Microscopy and X-ray Micro-Computed Tomography (2020)
Journal Article
Marr, N., Hopkinson, M., Hibbert, A., Pitsillides, A., & Thorpe, C. (2020). Bimodal Whole-Mount Imaging of Tendon Using Confocal Microscopy and X-ray Micro-Computed Tomography. Biological Procedures Online, https://doi.org/10.1186/s12575-020-00126-4

BACKGROUND:3-dimensional imaging modalities for optically dense connective tissues such as tendons are limited and typically have a single imaging methodological endpoint. Here, we have developed a bimodal procedure utilising fluorescence-based confo... Read More about Bimodal Whole-Mount Imaging of Tendon Using Confocal Microscopy and X-ray Micro-Computed Tomography.

Applied mechanical loading to mouse hindlimb acutely increases skeletal perfusion and chronically enhanced vascular porosity (2020)
Journal Article
Gohin, S., Javaheri, B., Hopkinson, M., Pitsillides, A. A., Arnett, T. R., & Chenu, C. (2020). Applied mechanical loading to mouse hindlimb acutely increases skeletal perfusion and chronically enhanced vascular porosity. Journal of Applied Physiology,

Blood supply is essential for osteogenesis, yet its relationship to load-related increases in bone mass is poorly defined. Herein, we aim to investigate the link between load-induced osteogenesis and the blood supply (bone perfusion and vascular poro... Read More about Applied mechanical loading to mouse hindlimb acutely increases skeletal perfusion and chronically enhanced vascular porosity.

Osteoarthritis-related nociceptive behaviour following mechanical joint loading correlates with cartilage damage (2020)
Journal Article
Ter Heegde, F., Luiz, A. P., Santana-Varela, S., Magnusdottir, R., Hopkinson, M., Chang, Y. M., …Chenu, C. (2020). Osteoarthritis-related nociceptive behaviour following mechanical joint loading correlates with cartilage damage. Osteoarthritis and Cartilage, 28(3), 383-395. https://doi.org/10.1016/j.joca.2019.12.004

In osteoarthritis (OA), the pain-structure relationship remains complex and poorly understood. Here, we used the mechanical joint loading (MJL) model of OA to investigate both knee pathology and nociceptive behaviour.

Conditional deletion of E11/Podoplanin in bone protects against ovariectomy-induced increases in osteoclast formation and activity (2020)
Journal Article
Staines, K., Hopkinson, M., Dillon, S., Stephen, L., Fleming, R., Sophocleous, A., …Farquharson, C. (2020). Conditional deletion of E11/Podoplanin in bone protects against ovariectomy-induced increases in osteoclast formation and activity. Bioscience Reports, 40, https://doi.org/10.1042/BSR20190329

E11/Podoplanin (Pdpn) is implicated in early osteocytogenesis and the formation of osteocyte dendrites. This dendritic network is critical for bone modelling/remodelling, through the production of receptor activator of nuclear factor κ B (RANK)-ligan... Read More about Conditional deletion of E11/Podoplanin in bone protects against ovariectomy-induced increases in osteoclast formation and activity.

Sost haploinsufficiency provokes peracute lethal cardiac tamponade without rescuing the osteopenia in a mouse model of excess glucocorticoids (2019)
Journal Article
Javaheri, B., Herbert, E., Hopkinson, M., Al-Jazzar, A., & Pitsillides, A. A. (2019). Sost haploinsufficiency provokes peracute lethal cardiac tamponade without rescuing the osteopenia in a mouse model of excess glucocorticoids. American Journal of Pathology, 189(4), 753-761. https://doi.org/10.1016/j.ajpath.2018.12.007

Glucocorticoid-induced secondary osteoporosis is the most predictable side-effect of this anti-inflammatory. One of the main mechanisms by which glucocorticoids achieve such deleterious outcome in bone is by antagonizing Wnt/β-catenin signalling. Scl... Read More about Sost haploinsufficiency provokes peracute lethal cardiac tamponade without rescuing the osteopenia in a mouse model of excess glucocorticoids.

Sexually dimorphic tibia shape is linked to natural osteoarthritis in STR/Ort mice (2018)
Journal Article
Javaheri, B., Razi, H., Piles, M., De Souza, R., Chang, Y. M., Maric-Mur, I., …Pitsillides, A. A. (2018). Sexually dimorphic tibia shape is linked to natural osteoarthritis in STR/Ort mice. Osteoarthritis and Cartilage, 26(6), 807-817. https://doi.org/10.1016/j.joca.2018.03.008

Human osteoarthritis (OA) is detected only at late stages. Male STR/Ort mice develop knee OA spontaneously with known longitudinal trajectory, offering scope to identify OA predisposing factors. We exploit the lack of overt OA in female STR/Ort and i... Read More about Sexually dimorphic tibia shape is linked to natural osteoarthritis in STR/Ort mice.

Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis (2017)
Journal Article
Javaheri, B., Poulet, B., Aljazzar, A., De Souza, R., Piles, M., Hopkinson, M., …Pitsillides, A. A. (2017). Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis. BONE, 103, 308-317. https://doi.org/10.1016/j.bone.2017.07.028

Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in protecting against such chronic disorders have been examined previously. Sulforap... Read More about Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis.

Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation (2017)
Journal Article
Staines, K. A., Javaheri, B., Hohenstein, P., Fleming, R., Ikpegbu, E., Unger, E., …Farquharson, C. (2017). Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation. Journal of Cellular Physiology, 232(11), 3006-3019. https://doi.org/10.1002/jcp.25999

The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by gl... Read More about Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation.

Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues (2017)
Journal Article
Al-Jazzar, A., Javaheri, B., Prideaux, M., Boyde, A., Scudamore, C. L., Cherifi, C., …Pitsillides, A. A. (2017). Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues. International Journal of Molecular Sciences, 18(1), https://doi.org/10.3390/ijms18010029

Mice harbouring a dentin matrix protein 1 (Dmp1) promoter-driven human diphtheria toxin (DT) receptor (HDTR) transgene (Tg) have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT) treatment in order to define osteoc... Read More about Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues.

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window? (2016)
Journal Article
Hildyard, J. C. W., Lacey, E., Booler, H., Hopkinson, M., Wells, D. J., & Brown, S. C. (2016). Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?. PLoS ONE, 11(7), e0159853. https://doi.org/10.1371/journal.pone.0159853

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular d... Read More about Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?.

Degree of Cajal-Retzius cell mislocalisation correlates with the severity of structural brain defects in mouse models of dystroglycanopathy (2016)
Journal Article
Booler, H., Williams, J., Hopkinson, M., & Brown, S. C. (2016). Degree of Cajal-Retzius cell mislocalisation correlates with the severity of structural brain defects in mouse models of dystroglycanopathy. Brain Pathology, 26(4), 465-478. https://doi.org/10.1111/bpa.12306

The secondary dystroglycanopathies are characterized by the hypoglycosylation of alpha dystroglycan, and are associated with mutations in at least 18 genes that act on the glycosylation of this cell surface receptor rather than the Dag1 gene itself.... Read More about Degree of Cajal-Retzius cell mislocalisation correlates with the severity of structural brain defects in mouse models of dystroglycanopathy.