Selective inhibition of RANK blocks osteoclast maturation
Regulation of the formation and function of bone-resorbing osteoclasts is a key to understanding the pathogenesis of skeletal disorders. Gene-targeting studies have shown that the RANK signaling pathway plays a critical role in osteoclast differentiation and function. Although pharmaceutical blockade of RANK may be a viable strategy for preventing bone destruction, RANK is implicated in multiple biological processes. Recently, a cytoplasmic motif of RANK was identified that may be specifically involved in osteoclast differentiation. In a recent study [1], the authors developed a cell-permeable inhibitor termed the RANK receptor inhibitor (RRI), which targets this motif.
How does body fat influence bone mass in childhood?
Fat mass may be a causal determinant of bone mass, but the evidence is conflicting, possibly reflecting the influence of confounding factors. The recent identification of common genetic variants related to obesity in children provides an opportunity to implement a Mendelian randomization study of obesity and bone outcomes, which is less subject to confounding and several biases than conventional approaches. Genotyping was retrieved for variants of two loci reliably associated with adiposity (the fat mass and obesity-related gene FTO and that upstream of the MC4R locus) within 7470 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had undergone total body DXA scans at a mean of 9.9 yr [1]. Relationships between both fat mass/genotypes and bone measures were assessed in efforts to determine evidence of causality between adiposity and bone mass.
Oxytocin is an anabolic bone hormone
Oxytocin, a hypothalamic nanopeptide secreted into the circulation from the posterior pituitary, is indispensable for lactation. It acts on a G protein-coupled receptor, the expression of which in reproductive tissues is regulated by sex steroids and oxytocin itself. In humans and rodents, plasma oxytocin levels are elevated maximally during suckling.
Activation of renin–angiotensin system induces osteoporosis
Hypertension and osteoporosis are two major age-related disorders; however, the underlying molecular mechanism for this comorbidity is not known. The renin–angiotensin system (RAS) plays a central role in the control of blood pressure and has been an important target of antihypertensive drugs. Using a chimeric RAS model of transgenic THM (Tsukuba hypertensive mouse) expressing both the human renin and human angiotensinogen genes, the authors of a recent study [1] showed that activation of RAS induces high turnover osteoporosis with accelerated bone resorption.
Systemic injection of engineered stem cells restores bone mass
Transplantation of gene-modified mesenchymal stem cells (MSCs) in animals for bone regeneration therapy has been evaluated extensively in recent years. However, increased endosteal bone formation by intravenous injection of MSCs ectopically expressing a foreign gene has not yet been shown. Aside from the clearance by lung and other tissues, the surface compositions of MSCs may not favor their bone marrow (BM) migration and engraftment.
 Download here the slide set presented by Prof. Friedlander, on Thursday, November 10th. |
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