Accès ouvert
2026
article
OpenAlex
Leah Wells, Jacob Keen, Aikta Sharma, Neil Marr et autres
Chondrocyte hypertrophy is a key hallmark of osteoarthritis (OA) that drives a multitude of whole-joint disease processes. There are no approved disease-modifying pharmaceuticals in clinical use, emphasising the urgent need for innovative therapeutics. Screening of a focussed chemical library using a novel …
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Accès ouvert
2026
article
OpenAlex
T. Dreyer, Eleanor Gouldie, Jacob Keen, Phil Salmon et autres
Facial paralysis, hearing loss and potentially lethal raised intracranial pressure are primary symptoms of sclerosteosis, an ultra-rare, autosomal recessive high bone mass (HBM) condition that predominantly manifests in skull pathologies. Non-invasive treatment remains an unmet clinical need. Recently, PORCN inhibition has been …
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Accès ouvert
2026
preprint
OpenAlex
Lucie E. Bourne, Aikta Sharma, Scott Dillon, Jacob 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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Accès ouvert
2025
article
OpenAlex
Jacob Trend, Jacob Keen, Aikta Sharma, Alisha Sharma et autres
Cortical bone is highly porous and composed of an interconnecting network of vascular canals and osteocyte lacunae. Our understanding of the mechanisms coupling vascular: lacunar spatial organisation in cortical bone is poorly understood. Defining cellular cross-talk mechanisms could be key in identification …
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Accès ouvert
2025
article
OpenAlex
Fabio A. Simoes, Greg Scutt, Manuela Mengozzi, Simon Mitchell et autres
OBJECTIVE: Therapeutic potential of selective aggrecanase inhibition in osteoarthritis (OA) was previously demonstrated using a variant of endogenous tissue inhibitor of metalloproteinase-3 (TIMP-3); however, this relied on transgenic mice overexpressing TIMP-3. Here, we develop a translational approach for harnessing the aggrecanase-selective inhibitory …
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Accès ouvert
2025
article
OpenAlex
T. Dreyer, Jacob Keen, Leah Wells, Mark Hopkinson et autres
Abstract Sclerosteosis, an ultra-rare disorder characterised by high bone mass (HBM) and skeletal overgrowth, leads to facial paralysis, hearing loss and raised intracranial pressure, which is currently managed only through high-risk surgery. Sclerosteosis is caused by SOST mutations and loss of functional …
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Accès ouvert
2023
article
OpenAlex
Lucie E. Bourne, Bethan K. Davies, José Luís Millán, Timothy R. Arnett et autres
Extracellular pyrophosphate (PPi) is well known for its fundamental role as a physiochemical mineralisation inhibitor. However, information about its direct actions on bone cells remains limited. This study shows that PPi decreased osteoclast formation and resorptive activity by ≤50 %. These inhibitory …
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Accès ouvert
2023
article
OpenAlex
T. Dreyer, Jacob Keen, Leah Wells, Scott J. Roberts
As a key regulator of bone homeostasis, sclerostin has garnered a lot of interest over the last two decades. Although sclerostin is primarily expressed by osteocytes and is well known for its role in bone formation and remodelling, it is also expressed …
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