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The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability (2022)
Journal Article
Samvelyan, H. J., Huesa, C., Cui, L., Farquharson, C., & Staines, K. A. (2022). The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability. Bone & Joint Research, 11(3), 162-170. https://doi.org/10.1302/2046-3758.113.bjr-2021-0259.r1

Aims Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA develop... Read More about The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability.

Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro (2021)
Journal Article
Staines, K. A., Myers, K., Little, K., Ralston, S. H., & Farquharson, C. (2021). Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro. Calcified Tissue International, 109, 696-705. https://doi.org/10.1007/s00223-021-00882-9

Proton pump inhibitors (PPIs) have been associated with an increased risk of fragility fractures in pharmaco-epidemiological studies. The mechanism is unclear, but it has been speculated that by neutralising gastric acid, they may reduce intestinal c... Read More about Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro.

Ubiquitin-protein ligase Ubr5 cooperates with hedgehog signalling to promote skeletal tissue homeostasis (2021)
Journal Article
Mellis, D., Staines, K. A., Peluso, S., Georgiou, I. C., Dora, N., Kubiak, M., …Ditzel, M. (2021). Ubiquitin-protein ligase Ubr5 cooperates with hedgehog signalling to promote skeletal tissue homeostasis. PLoS Genetics, 17(4), Article e1009275. https://doi.org/10.1371/journal.pgen.1009275

Mammalian Hedgehog (HH) signalling pathway plays an essential role in tissue homeostasis and its deregulation is linked to rheumatological disorders. UBR5 is the mammalian homologue of the E3 ubiquitin-protein ligase Hyd, a negative regulator of the... Read More about Ubiquitin-protein ligase Ubr5 cooperates with hedgehog signalling to promote skeletal tissue homeostasis.

Life course longitudinal growth and risk of knee osteoarthritis at age 53 years: evidence from the 1946 British birth cohort study (2020)
Journal Article
Staines, K. A., Hardy, R., Samvelyan, H. J., Ward, K. A., & Cooper, R. (2021). Life course longitudinal growth and risk of knee osteoarthritis at age 53 years: evidence from the 1946 British birth cohort study. Osteoarthritis and Cartilage, 29(3), 335-340. https://doi.org/10.1016/j.joca.2020.12.012

Objective To examine the relationship between height gain across childhood and adolescence with knee osteoarthritis in the MRC National Survey of Health and Development (NSHD). Materials and methods Data are from 3035 male and female participant... Read More about Life course longitudinal growth and risk of knee osteoarthritis at age 53 years: evidence from the 1946 British birth cohort study.

Zinc ameliorates human aortic valve calcification through GPR39 mediated ERK1/2 signalling pathway (2020)
Journal Article
Chen, Z., Gordillo-Martinez, F., Jiang, L., He, P., Hong, W., Wei, X., …Zhu, D. (2021). Zinc ameliorates human aortic valve calcification through GPR39 mediated ERK1/2 signalling pathway. Cardiovascular Research, 117(3), 820-835. https://doi.org/10.1093/cvr/cvaa090

Aims Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. It has been reported that zinc is accumulated in calcified human aortic valves. However, whether zinc directly regulates CAVD is yet to be elucida... Read More about Zinc ameliorates human aortic valve calcification through GPR39 mediated ERK1/2 signalling pathway.

Models of osteoarthritis: relevance and new insights (2020)
Journal Article
Samvelyan, H., Hughes, D., Stevens, C., & Staines, K. A. (2021). Models of osteoarthritis: relevance and new insights. Calcified Tissue International, 109(3), 243-256. https://doi.org/10.1007/s00223-020-00670-x

Osteoarthritis (OA) is a progressive and disabling musculoskeletal disease affecting millions of people and resulting in major healthcare costs worldwide. It is the most common form of arthritis, characterised by degradation of the articular cartilag... Read More about Models of osteoarthritis: relevance and new insights.

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(1), 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 modeling/remodeling, through the production of the receptor for receptor activator of nuclear factor κ... Read More about Conditional deletion of E11/Podoplanin in bone protects against ovariectomy-induced increases in osteoclast formation and activity.

Azathioprine Has a Deleterious Effect on the Bone Health of Mice with DSS-Induced Inflammatory Bowel Disease (2019)
Journal Article
Morgan, S., Hooper, K. M., Milne, E. M., Farquharson, C., Stevens, C., & Staines, K. A. (2019). Azathioprine Has a Deleterious Effect on the Bone Health of Mice with DSS-Induced Inflammatory Bowel Disease. International Journal of Molecular Sciences, 20(23), Article 6085. https://doi.org/10.3390/ijms20236085

Patients with inflammatory bowel disease (IBD) often present poor bone health and are 40% more at risk of bone fracture. Studies have implicated autophagy in IBD pathology and drugs used to treat IBD stimulate autophagy in varying degrees, however, t... Read More about Azathioprine Has a Deleterious Effect on the Bone Health of Mice with DSS-Induced Inflammatory Bowel Disease.

In situ characterization of nanoscale strains in loaded whole joints via synchrotron X-ray tomography (2019)
Journal Article
Madi, K., Staines, K., Bay, B., Javaheri, B., Geng, H., Bodey, A., …Lee, P. (2020). In situ characterization of nanoscale strains in loaded whole joints via synchrotron X-ray tomography. Nature Biomedical Engineering, 4(3), 343-354. https://doi.org/10.1038/s41551-019-0477-1

Imaging techniques for quantifying changes in the hierarchical structure of deforming joints are constrained by destructive sample treatments, sample-size restrictions and lengthy scan times. Here, we report the use of fast low-dose pink-beam synchro... Read More about In situ characterization of nanoscale strains in loaded whole joints via synchrotron X-ray tomography.

Raman spectroscopy links differentiating osteoblast matrix signatures to pro-angiogenic potential (2019)
Journal Article
Sharma, A., Goring, A., Staines, K., Emery, R., Pitsillides, A. A., Oreffo, R. O., …Clarkin, C. E. (2020). Raman spectroscopy links differentiating osteoblast matrix signatures to pro-angiogenic potential. Matrix Biology Plus, 5, https://doi.org/10.1016/j.mbplus.2019.100018

Mineralization of bone is achieved by the sequential maturation of the immature amorphous calcium phase to mature hydroxyapatite and is central to the process of bone development and repair. To study normal and dysregulated mineralization in vitro, s... Read More about Raman spectroscopy links differentiating osteoblast matrix signatures to pro-angiogenic potential.

Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis (2019)
Journal Article
Staines, K., Ikpegbu, E., Törnqvist, A., Dillon, S., Javaheri, B., Amin, A. K., …Farquharson, C. (2019). Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis. BMC Musculoskeletal Disorders, 20, Article 344 (2019). https://doi.org/10.1186/s12891-019-2731-9

Background: Subchondral bone (SCB) thickening is one of the earliest detectable changes in osteoarthritic joints and is considered a potential trigger for subsequent articular cartilage degeneration. In this manuscript, we examine whether disruption... Read More about Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis.

How to build a bone: PHOSPHO1, biomineralization and beyond (2019)
Journal Article
Dillon, S., Staines, K. A., Millán, J. L., & Farquharson, C. (2019). How to build a bone: PHOSPHO1, biomineralization and beyond. Journal of Bone and Mineral Research Plus, 3(7), Article e10202. https://doi.org/10.1002/jbm4.10202

Since its characterization two decades ago, the phosphatase PHOSPHO1 has been the subject of an increasing focus of research. This work has elucidated PHOSPHO1’s central role in the biomineralization of bone and other hard tissues, but has also impli... Read More about How to build a bone: PHOSPHO1, biomineralization and beyond.

The inflammatory bowel disease drug azathioprine induces autophagy via mTORC1 and the unfolded protein response sensor PERK (2019)
Journal Article
Hooper, K. M., Casanova, V., Kemp, S., Staines, K. A., Satsangi, J., Barlow, P. G., …Stevens, C. (2019). The inflammatory bowel disease drug azathioprine induces autophagy via mTORC1 and the unfolded protein response sensor PERK. Inflammatory Bowel Diseases, 25(9), 1481-1496. https://doi.org/10.1093/ibd/izz039

Background Genetic studies have strongly linked autophagy to Crohn's disease (CD) and stimulating autophagy in CD patients may be therapeutically beneficial. The aim of this study was to evaluate the effect of current inflammatory bowel disease (IBD)... Read More about The inflammatory bowel disease drug azathioprine induces autophagy via mTORC1 and the unfolded protein response sensor PERK.

The Ex Vivo Organ Culture of Bone (2019)
Book Chapter
Staines, K. A., Brown, G., & Farquharson, C. (2019). The Ex Vivo Organ Culture of Bone. In Bone Research Protocols (199-215). New york, USA: Humana Press. https://doi.org/10.1007/978-1-4939-8997-3_10

The ex vivo organ culture of bone provides many of the advantages of both the whole organism and isolated cell strategies and can deliver valuable insight into the network of processes and activities that are fundamental to bone and cartilage biology... Read More about The Ex Vivo Organ Culture of Bone.

A Computed Microtomography Method for Understanding Epiphyseal Growth Plate Fusion (2018)
Journal Article
Staines, K. A., Lee, P. D., Pitsillides, A. A., Staines, K., Madi, K., Javaheri, B., …Pitsillides, A. (2018). A Computed Microtomography Method for Understanding Epiphyseal Growth Plate Fusion. Frontiers in Materials, 4, https://doi.org/10.3389/fmats.2017.00048

The epiphyseal growth plate is a developmental region responsible for linear bone growth, in which chondrocytes undertake a tightly regulated series of biological processes. Concomitant with the cessation of growth and sexual maturation, the human gr... Read More about A Computed Microtomography Method for Understanding Epiphyseal Growth Plate Fusion.

FGF-2 promotes osteocyte differentiation through increased E11/podoplanin expression (2017)
Journal Article
Ikpegbu, E., Basta, L., Clements, D. N., Fleming, R., Vincent, T. L., Buttle, D. J., …Farquharson, C. (2018). FGF-2 promotes osteocyte differentiation through increased E11/podoplanin expression. Journal of Cellular Physiology, 233(7), 5334-5347. https://doi.org/10.1002/jcp.26345

E11/podoplanin is critical in the early stages of osteoblast-to-osteocyte transitions (osteocytogenesis) however the upstream events which regulate E11 expression are unknown. The aim of this study was to examine the effects of FGF-2 on E11-mediated... Read More about FGF-2 promotes osteocyte differentiation through increased E11/podoplanin expression.

Sost deficiency does not alter bone’s lacunar or vascular porosity in mice (2017)
Journal Article
Mosey, H., Núñez, J. A., Goring, A., Clarkin, C. E., Staines, K. A., Lee, P. D., …Javaheri, B. (2017). Sost deficiency does not alter bone’s lacunar or vascular porosity in mice. Frontiers in Materials, 4, Article 27. https://doi.org/10.3389/fmats.2017.00027

SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key reg... Read More about Sost deficiency does not alter bone’s lacunar or vascular porosity in mice.

A distinctive patchy osteomalacia characterises Phospho1 -deficient mice (2017)
Journal Article
-deficient mice. Journal of Anatomy, 231(2), 298-308. https://doi.org/10.1111/joa.12628

The phosphatase PHOSPHO1 is involved in the initiation of biomineralisation. Bones in Phospho1 KO mice show histological osteomalacia with frequent bowing of long bones and spontaneous fractures: they contain less mineral, with smaller mineral crysta... Read More about A distinctive patchy osteomalacia characterises Phospho1 -deficient mice.

Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation (2017)
Journal Article
Buttle, D. J., Pitsillides, A. A., Staines, K. A., Javaheri, B., Hohenstein, P., Fleming, R., …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.

Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity (2016)
Journal Article
Poulet, B., Liu, K., Plumb, D., Vo, P., Shah, M., Staines, K., …Bou-Gharios, G. (2016). Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity. PLOS ONE, 11(12), Article e0167971. https://doi.org/10.1371/journal.pone.0167971

Bone development and length relies on the growth plate formation, which is dependent on degradative enzymes such as MMPs. Indeed, deletion of specific members of this enzyme family in mice results in important joint and bone abnormalities, suggesting... Read More about Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity.