Bone Abstracts

Background: Cannabinoid receptors are expressed in synovial joints but their role in joint disease is unknown. Here we examined the role of the type 2 cannabinoid receptor (CB2) in the pathogenesis of age-related osteoarthritis and osteoarthritis caused by destabilisation of the medial meniscus (DMM) in WT and CB2-deficient mice (Cnr2−/− mice).Methods: The severity of arthritis was graded histologically according to standard techni...

Fibroblast growth factor-23 (FGF23) controls serum phosphorus by acting on the kidneys to excrete phosphorus and reduce calcitriol. These actions are well established in adults and children, but whether FGF23 regulates fetal phosphorus metabolism is unknown. We used X-linked Hyp or Phex null male fetuses to study the effect of excess FGF23 on fetal phosphorus metabolism. Phex+/− females and WT males were mated to generate WT, Phe...

Lack of Klotho, the co-receptor for the bone-derived hormone fibroblast growth factor-23 (FGF23), leads to a severe impairment in bone mineralization in mice. However, the mechanisms underlying the Klotho deficiency-associated defects in bone mineralization are still poorly understood. Here, we sought to elucidate the vitamin D independent role of Klotho in bone mineralization. To ablate increased vitamin D signaling in Klotho knockout mice (Kl−/−), we c...

Fibroblast growth factor-23 (FGF23) is a hormone originating from osteocytes with suppressive actions on renal phosphate reabsorption and vitamin D synthesis. We recently identified FGF23 as a calcium-conserving hormone, regulating the membrane transport of the epithelial calcium channel TRPV5 in distal renal tubules. Here, we analyzed the long term sequelae of Fgf23 deficiency and renal calcium wasting on bone and mineral metabolism in 9-month-old mice lacking both Fgf23<...

Fractures are very common and affect 2% of the population per annum. Fragility fractures represent the greatest unmet need and are associated with high rates of morbidity and mortality. Currently, there is no approved therapy for enhancing healing of fragility fractures. We previously reported that upregulation of the early inflammatory response following skeletal injury can promote fracture repair (Glass et al PNAS 2011). Inflammation represents the earliest response followin...

Recent studies have demonstrated that the global or osteoblast-specific deletion of neuropeptide Y Y1 receptor (Y1R), as well as the pharmacological blockade of Y1R, leads to pronounced anabolic effects in bone metabolism. This suggests that anti-Y1R drug therapy might have clinical applications for the prevention/recovery of bone loss occurring in osteoporosis. Given the high fracture incidence in this target population, it remained...