Physiological function of the renin-angiotensin system in bone remodeling

Vascular and bone biology have many features and regulatory mechanisms in common; both systems are subject to tissue remodeling in response to various physiologic and pathologic stimuli. As a result, osteoporosis and vascular disease often coincide in the elderly, with the most common associations being elevated blood pressure, calcification of the vascular wall, and reduced bone mineral density.

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Adipocyte-secreted factors and higher bone mass in obese people

Several studies have reported controversial results about the positive correlation between the body fat mass and bone mineral density. It remains unclear whether some adipocyte-secreted factors can act on bone metabolism, directly on osteoblasts, to favor bone formation or osteoclasts, which control bone resorption. The authors of this study [1] investigated the effect of fat cell secreted molecules on proliferation and differentiation of preosteoblasts.

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Evidence for osteocyte regulation of bone homeostasis through RANKL expression

Agrowing number of evidence suggests that osteocytes orchestrate bone homeostasis by regulating the number and activity of bone-forming osteoblasts and bone-resorbing osteoclasts.
Using cell fractionation and purification techniques, the authors of this study [1] demonstrated that osteocytes produced larger amounts of RANKL mRNA than osteoblasts.
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Lrp5 functions in bone to regulate bone mass

The human skeleton is affected by mutations in low-density lipoprotein receptor-related protein 5 (LRP5). Mutations of this LRP5 lead to dominant high bone mass (HBM) syndrome. To understand how LRP5 influences bone properties, the authors generated transgenic mice with knockin or knockout mutation of the LRP5 gene. Depending on the strain studied, the mutation was specifically localized in the osteocytes, the gut, or the appendicular skeleton.

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Matrix-embedded cells control osteoclast formation

Osteoclast activity is crucial for bone growth during development by resorbing calcified cartilage produced by chondrocytes. Bone-resorbing activity is also important for bone remodeling throughout mammalian life. Osteoclast differentiation is mediated by the cytokine receptor activator of nuclear factor κ-B ligand (RANKL). However, RANKL is expressed by a variety of cell types and it is still unclear which cells are essential sources for RANKL synthesis and thus for osteoclastogenesis.

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