Vascular biology and bone formation: hints from HIF

Abstract

In this issue of the JCI, Wang, Clemens, and colleagues demonstrate that hypoxia-inducible factor α (HIFα) signaling in bone-building osteoblasts is central to the coupling of angiogenesis and long bone development in mice (see the related article beginning on page 1616). They show that bone formation controlled by osteoblast HIFα signaling is not cell autonomous but is coupled to skeletal angiogenesis dependent upon VEGF signaling. Thus, strategies that promote HIFα signaling in osteoblasts may augment bone formation and accelerate fracture repair.

Vascular Calcification

“…56 The processes directing true ossification may relate to angiogenic signals provided by hypoxia induced factor ␣ and vascular endothelial growth factor, important mediators of bone formation and osteogenic-angiogenic coupling. 57 …”

Difference in intraosseous blood vessel volume and number in osteoporotic model mice induced by spinal cord injury and sciatic nerve resection

“…We also want to make a clear distinction on the pathogenesis of osteoporosis after SCI and disuse osteoporosis through inspecting intraosseous blood vessel volume and number. Although the importance of local blood supply in bone formation and healing has been well established [10][11][12], the effect of intraosseous blood vessels on osteoporosis is largely unknown and usually only reported in old ageassociated osteoporosis [13][14][15]; the use of microcomputed tomography (lCT) in analysis of intraosseous blood vessel parameters in an osteoporotic model induced by nerve injury has not been reported.…”

Facilitation of human osteoblast apoptosis by sulindac and indomethacin under hypoxic injury

“…In fractured bone, the hypoxia-inducible factor (HIF) signaling pathway will be induced when circulation to a fractured region is blocked [Towler, 2007]. HIF-1a, a heterodimer that functions as a transcription factor, is tightly regulated at the protein level under normoxic conditions through ubiquitin-mediated degradation and is stabilized and activated under conditions of hypoxia [Komatsu and Hadjiargyrou, 2004].…”