Search Results
You are looking at 1 - 10 of 10 items for
- Author: Colin Farquharson x
- Refine by access: All content x
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
In this issue of Journal of Endocrinology, Lanham et al. investigated the effects of hypothyroidism on the developing skeleton of the ovine foetus in utero. Their analyses indicated that, following thyroidectomy, bone growth, structure and mechanical properties were all altered at late gestation or at term. Adrenalectomy, whilst preventing the prepartum rise in triiodothyronine, did not modify skeletal development. The hypothyroid-mediated skeletal defects of the developing foetus described in this study may have clinical implications for bone health in later life.
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
Search for other papers by Katherine Staines in
Google Scholar
PubMed
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
Search for other papers by Ruth Andrew in
Google Scholar
PubMed
Search for other papers by Katherine A Staines in
Google Scholar
PubMed
Search for other papers by Vicky E MacRae in
Google Scholar
PubMed
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
Search for other papers by Katherine A Staines in
Google Scholar
PubMed
Search for other papers by Vicky E MacRae in
Google Scholar
PubMed
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
The small integrin-binding ligand N-linked glycoprotein (SIBLING) family consists of osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. These proteins share many structural characteristics and are primarily located in bone and dentin. Accumulating evidence has implicated the SIBLING proteins in matrix mineralisation. Therefore, in this review, we discuss the individual role that each of the SIBLING proteins has in this highly orchestrated process. In particular, we emphasise how the nature and extent of their proteolytic processing and post-translational modification affect their functional role. Finally, we describe the likely roles of the SIBLING proteins in clinical disorders of hypophosphataemia and their potential therapeutic use.
Search for other papers by Fiona Roberts in
Google Scholar
PubMed
Search for other papers by Greg Markby in
Google Scholar
PubMed
Search for other papers by Scott Dillon in
Google Scholar
PubMed
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
Search for other papers by Vicky E MacRae in
Google Scholar
PubMed
The physiological mineralisation of skeletal tissues, as well as the pathological mineralisation of soft tissues involves a fine balance between regulators that either promote or inhibit the process. In recent years, several studies have advocated a non-skeletal role for some of these mineralisation regulators in a range of human diseases, including diabetes, cardiovascular disease, obesity and neurodegenerative disease. This is an emerging area of interest and the functional roles and mechanisms of action of these various endocrine factors, phosphatases and phosphodiesterase’s in important pathologies are the focus of this review. Mechanistic insight of the pathways through which these acknowledged regulators of skeletal mineralisation act beyond the skeleton has the potential to identify druggable targets for commonly experienced morbidities, notably those related to metabolism and metabolic syndrome.
Search for other papers by Karla J Suchacki in
Google Scholar
PubMed
Search for other papers by Fiona Roberts in
Google Scholar
PubMed
Search for other papers by Andrea Lovdel in
Google Scholar
PubMed
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
Search for other papers by Nik M Morton in
Google Scholar
PubMed
Search for other papers by Vicky E MacRae in
Google Scholar
PubMed
Search for other papers by William P Cawthorn in
Google Scholar
PubMed
Throughout the last decade, significant developments in cellular, molecular and mouse models have revealed major endocrine functions of the skeleton. More recent studies have evolved the interplay between bone-specific hormones, the skeleton, marrow adipose tissue, muscle and the brain. This review focuses on literature from the last decade, addressing the endocrine regulation of global energy metabolism via the skeleton. In addition, we will highlight several recent studies that further our knowledge of new endocrine functions of some organs; explore remaining unanswered questions; and, finally, we will discuss future directions for this more complex era of bone biology research.
Search for other papers by Claire L Wood in
Google Scholar
PubMed
Department of Women’s and Children’s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, Stockholm, Sweden
Search for other papers by Ondrej Soucek in
Google Scholar
PubMed
Search for other papers by Sze C Wong in
Google Scholar
PubMed
Search for other papers by Farasat Zaman in
Google Scholar
PubMed
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
Search for other papers by Lars Savendahl in
Google Scholar
PubMed
Search for other papers by S Faisal Ahmed in
Google Scholar
PubMed
Glucocorticoids (GCs) are effective for the treatment of many chronic conditions, but their use is associated with frequent and wide-ranging adverse effects including osteoporosis and growth retardation. The mechanisms that underlie the undesirable effects of GCs on skeletal development are unclear, and there is no proven effective treatment to combat them. An in vivo model that investigates the development and progression of GC-induced changes in bone is, therefore, important and a well-characterized pre-clinical model is vital for the evaluation of new interventions. Currently, there is no established animal model to investigate GC effects on skeletal development and there are pros and cons to consider with the different protocols used to induce osteoporosis and growth retardation. This review will summarize the literature and highlight the models and techniques employed in experimental studies to date.
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
Search for other papers by Claire L Wood in
Google Scholar
PubMed
Search for other papers by Rob van ‘t Hof in
Google Scholar
PubMed
Search for other papers by Scott Dillon in
Google Scholar
PubMed
Search for other papers by Volker Straub in
Google Scholar
PubMed
Search for other papers by Sze C Wong in
Google Scholar
PubMed
Search for other papers by S Faisal Ahmed in
Google Scholar
PubMed
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
Short stature and osteoporosis are common in Duchenne muscular dystrophy (DMD) and its pathophysiology may include an abnormality of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, which is further exacerbated by long-term glucocorticoid (GC) treatment. Hence, an agent that has anabolic properties and may improve linear growth would be beneficial in this setting and therefore requires further exploration. A 5-week-old x-linked muscular dystrophy (mdx) mice were used as a model of DMD. They were treated with prednisolone ± GH + IGF-1 for 4 weeks and then compared to control mdx mice to allow the study of both growth and skeletal structure. GC reduced cortical bone area, bone fraction, tissue area and volume and cortical bone volume, as assessed by micro computed tomography (CT) In addition, GC caused somatic and skeletal growth retardation but improved grip strength. The addition of GH + IGF-1 therapy rescued the somatic growth retardation and induced additional improvements in grip strength (16.9% increase, P < 0.05 compared to control). There was no improvement in bone microarchitecture (assessed by micro-CT and static histomorphometry) or biomechanical properties (assessed by three-point bending). Serum bone turnover markers (Serum procollagen 1 intact N-terminal propeptide (P1NP), alpha C-terminal telopeptide (αCTX)) also remained unaffected. Further work is needed to maximise these gains before proceeding to clinical trials in boys with DMD.
Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Search for other papers by Shun-Neng Hsu in
Google Scholar
PubMed
Search for other papers by Louise A Stephen in
Google Scholar
PubMed
Search for other papers by Scott Dillon in
Google Scholar
PubMed
Search for other papers by Elspeth Milne in
Google Scholar
PubMed
Search for other papers by Behzad Javaheri in
Google Scholar
PubMed
Search for other papers by Andrew A Pitsillides in
Google Scholar
PubMed
Search for other papers by Amanda Novak in
Google Scholar
PubMed
Search for other papers by Jose Luis Millán in
Google Scholar
PubMed
Search for other papers by Vicky E MacRae in
Google Scholar
PubMed
Search for other papers by Katherine A Staines in
Google Scholar
PubMed
Search for other papers by Colin Farquharson in
Google Scholar
PubMed
Patients with advanced chronic kidney disease (CKD) often present with skeletal abnormalities, a condition known as renal osteodystrophy (ROD). While tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 are critical for bone mineralization, their role in the etiology of ROD is unclear. To address this, ROD was induced in both WT and Phospho1 knockout (P1KO) mice through dietary adenine supplementation. The mice presented with hyperphosphatemia, hyperparathyroidism, and elevated levels of FGF23 and bone turnover markers. In particular, we noted that in CKD mice, bone mineral density (BMD) was increased in cortical bone (P < 0.05) but decreased in trabecular bone (P < 0.05). These changes were accompanied by decreased TNAP (P < 0.01) and increased PHOSPHO1 (P < 0.001) expression in WT CKD bones. In P1KO CKD mice, the cortical BMD phenotype was rescued, suggesting that the increased cortical BMD of CKD mice was driven by increased PHOSPHO1 expression. Other structural parameters were also improved in P1KO CKD mice. We further investigated the driver of the mineralization defects, by studying the effects of FGF23, PTH, and phosphate administration on PHOSPHO1 and TNAP expression by primary murine osteoblasts. We found both PHOSPHO1 and TNAP expressions to be downregulated in response to phosphate and PTH. The in vitro data suggest that the TNAP reduction in CKD-MBD is driven by the hyperphosphatemia and/or hyperparathyroidism noted in these mice, while the higher PHOSPHO1 expression may be a compensatory mechanism. Increased PHOSPHO1 expression in ROD may contribute to the disordered skeletal mineralization characteristic of this progressive disorder.
