Deposition of collagen type I onto skeletal endothelium reveals a new role for blood vessels in regulating bone morphology

Abstract

Recently, blood vessels have been implicated in the morphogenesis of various organs. The vasculature is also known to be essential for endochondral bone development, yet the underlying mechanism has remained elusive. We show that a unique composition of blood vessels facilitates the role of the endothelium in bone mineralization and morphogenesis. Immunostaining and electron microscopy showed that the endothelium in developing bones lacks basement membrane, which normally isolates the blood vessel from its surroundings. Further analysis revealed the presence of collagen type I on the endothelial wall of these vessels. Because collagen type I is the main component of the osteoid, we hypothesized that the bone vasculature guides the formation of the collagenous template and consequently of the mature bone. Indeed, some of the bone vessels were found to undergo mineralization. Moreover, the vascular pattern at each embryonic stage prefigured the mineral distribution pattern observed one day later. Finally, perturbation of vascular patterning by overexpressing Vegf in osteoblasts resulted in abnormal bone morphology, supporting a role for blood vessels in bone morphogenesis. These data reveal the unique composition of the endothelium in developing bones and indicate that vascular patterning plays a role in determining bone shape by forming a template for deposition of bone matrix.

The Potential of Several Fluoride-Based Varnishes as Remineralization Agents: Morphological Studies, Dentin Surface Hardness, and Crystallinity Tests

“…The results of the Mei study showed that SDF had a remineralization effect in increasing the dentin hardness [8], and this study used the same SDF concentration used here. SDF releases fluoride and helps the deposition of silver phosphate retain the mineral content while increasing the hardness of the dentin structure [20]. The remineralization effect in this study was seen from the increase in dentin hardness after the application of SDF.…”

“…The decrease in hardness is due to the loss of minerals such as calcium, phosphate, and magnesium. In addition, collagen degradation plays a role in mineral deposition [20]. The results of the Mei study showed that SDF had a remineralization effect in increasing the dentin hardness [8], and this study used the same SDF concentration used here.…”

Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes

“…Vascular invasion of the cartilage callus is an important step during endochondral repair (reviewed in Bahney et al, 2015) and fracture healing is significantly delayed when the vasculature is disrupted . Previous studies suggest that the endothelial cells enable degradation of the cartilage matrix by producing MMP-9 (Colnot et al, 2003;Wang et al, 2013), facilitate mineralization of the cartilage matrix by secreting BMPs (Bahney et al, 2014;Matsubara et al, 2012;Yu et al, 2010) and regulate deposition of collagen I (Ben Shoham et al, 2016).…”

Material‐Induced Venosome‐Supported Bone Tubes

“…A large majority of the blood vessels inside the scaffold were of small diameter (mainly less Adv. [22] SMA staining provided additional information as to the nature of the formed blood vessels, some displaying a thick SMA-stained layer (≈10 µm) indicative of arterioles and others presenting a thinner SMA-stained layer (>2 µm) were morphologically characteristic of venules, however no obvious zones containing exclusively one type of the other were observed. 2019, 6,1900844 .…”