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Bone vascular function and its importance for bone remodeling in health and disease

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Bone formation is dependent upon the vascular system. The vascular system is a functional component of bone and bone marrow since 1) bone marrow is the site of immune cell production, 2) blood vessels serve a role in hematopoietic stem cell niches, 3) skeletal perfusion has been associated with changes in ...

Bone formation is dependent upon the vascular system. The vascular system is a functional component of bone and bone marrow since 1) bone marrow is the site of immune cell production, 2) blood vessels serve a role in hematopoietic stem cell niches, 3) skeletal perfusion has been associated with changes in bone cellular metabolism, and 4) capillaries are components within bone basic multicellular units. During remodeling, bone marrow blood vessels are located next to sites of bone formation and, thus, this spatial location is critically important for bone development. It is imperative to understand that the etiologies of bone disease are multifactorial and that certain aspects may lie in the bone vasculature. Thus, proper regulation of the bone vascular network is vital to a healthy skeleton and dysregulation may contribute to osteopathology.

Osteopathology may derive a portion of its etiology from several vascular dysfunctions; i.e., diminished vasodilator and/or enhanced vasoconstrictor capacity of bone arteries/arterioles, reduced bone perfusion, angiogenesis/rarefaction, bone marrow blood vessel ossification and increased distance between bone marrow blood vessels and bone surfaces. Bone vascular dysfunction may rest internal to the skeleton (i.e., the bone marrow blood vessels) or external (i.e., nutrient arteries that originate outside and perforate the skeleton). Pathological conditions such as peripheral artery disease are linked to reduced bone mineral density and osteoporosis is associated with diminished bone blood flow and capillary rarefaction. For example, evidence indicate a clear relation between both reduced bone perfusion and bone arteriolar function, particularly through endothelium-dependent vasodilation, and diminished bone mass with aging. Interestingly, factors that regulate endothelium-dependent vasodilation (e.g., nitric oxide and prostacyclin) can diffuse into the bone interstitial space and directly modulate osteoblasts and osteoclasts. The bone vasculature can further modify bone cellular activity via modifications in bone interstitial fluid flow and pressure. In addition, intermittent parathyroid hormone administration, a common treatment for osteoporosis, alters the distance between bone marrow blood vessels and site of bone remodeling, which may impact bone accrual. It has been recently shown that bone marrow blood vessels ossify with advancing age and correspond with reduced patency. Finally, a common site for metastasis in certain forms of cancer (e.g., breast, lung and prostate) is the skeleton, with corresponding alterations in angiogenesis and potentially blood flow that may exacerbate the pathology.

Since vascular etiology of bone disease is poorly understood and understudied, this research topic is designed to coalesce information regarding the mechanisms by which the bone vascular network modulates bone mass and (re)modeling in health and disease. The research topics to be examined are the associations between bone mass and metabolism and 1) bone perfusion and the mechanisms of bone arteriolar function that regulate blood flow to the skeleton, 2) bone interstitial fluid flow and pressure, bone marrow blood vessel ossification and 4) bone marrow blood vessel spatial location and morphology via migration, angiogenesis and rarefaction. This research topic is in quest of perspectives, review and original research articles covering the interdependence of the bone vascular and skeletal systems in a variety of clinical scenarios (e.g., altered hormonal status or corrective therapies, age- and post-menopausal osteoporosis, bone metastasis, fracture repair, type 2 diabetes, sedentarism and physical activity).


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