TY - JOUR

T1 - Chronic Kidney Disease-Induced Vascular Calcification Impairs Bone Metabolism

AU - Mace, Maria L

AU - Gravesen, Eva

AU - Nordholm, Anders

AU - Egstrand, Soeren

AU - Morevati, Marya

AU - Nielsen, Carsten

AU - Kjaer, Andreas

AU - Behets, Geert

AU - D'Haese, Patrick

AU - Olgaard, Klaus

AU - Lewin, Ewa

N1 - © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

PY - 2021

Y1 - 2021

N2 - An association between lower bone mineral density (BMD) and presence of vascular calcification (VC) has been reported in several studies. Chronic kidney disease (CKD) causes detrimental disturbances in the mineral balance, bone turnover, and development of severe VC. Our group has previously demonstrated expression of Wnt inhibitors in calcified arteries of CKD rats. Therefore, we hypothesized that the CKD-induced VC via this pathway signals to bone and induces bone loss. To address this novel hypothesis, we developed a new animal model using isogenic aorta transplantation (ATx). Severely calcified aortas from uremic rats were transplanted into healthy rats (uremic ATx). Transplantation of normal aortas into healthy rats (normal ATx) and age-matched rats (control) served as control groups. Trabecular tissue mineral density, as measured by μCT, was significantly lower in uremic ATx rats compared with both control groups. Uremic ATx rats showed a significant upregulation of the mineralization inhibitors osteopontin and progressive ankylosis protein homolog in bone. In addition, we found significant changes in bone mRNA levels of several genes related to extracellular matrix, bone turnover, and Wnt signaling in uremic ATx rats, with no difference between normal ATx and control. The bone histomorphometry analysis showed significant lower osteoid area in uremic ATx compared with normal ATx along with a trend toward fewer osteoblasts as well as more osteoclasts in the erosion lacunae. Uremic ATx and normal ATx had similar trabecular number and thickness. The bone formation rate did not differ between the three groups. Plasma biochemistry, including sclerostin, kidney, and mineral parameters, were similar between all three groups. ex vivo cultures of aorta from uremic rats showed high secretion of the Wnt inhibitor sclerostin. In conclusion, the presence of VC lowers BMD, impairs bone metabolism, and affects several pathways in bone. The present results prove the existence of a vasculature to bone tissue cross-talk. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

AB - An association between lower bone mineral density (BMD) and presence of vascular calcification (VC) has been reported in several studies. Chronic kidney disease (CKD) causes detrimental disturbances in the mineral balance, bone turnover, and development of severe VC. Our group has previously demonstrated expression of Wnt inhibitors in calcified arteries of CKD rats. Therefore, we hypothesized that the CKD-induced VC via this pathway signals to bone and induces bone loss. To address this novel hypothesis, we developed a new animal model using isogenic aorta transplantation (ATx). Severely calcified aortas from uremic rats were transplanted into healthy rats (uremic ATx). Transplantation of normal aortas into healthy rats (normal ATx) and age-matched rats (control) served as control groups. Trabecular tissue mineral density, as measured by μCT, was significantly lower in uremic ATx rats compared with both control groups. Uremic ATx rats showed a significant upregulation of the mineralization inhibitors osteopontin and progressive ankylosis protein homolog in bone. In addition, we found significant changes in bone mRNA levels of several genes related to extracellular matrix, bone turnover, and Wnt signaling in uremic ATx rats, with no difference between normal ATx and control. The bone histomorphometry analysis showed significant lower osteoid area in uremic ATx compared with normal ATx along with a trend toward fewer osteoblasts as well as more osteoclasts in the erosion lacunae. Uremic ATx and normal ATx had similar trabecular number and thickness. The bone formation rate did not differ between the three groups. Plasma biochemistry, including sclerostin, kidney, and mineral parameters, were similar between all three groups. ex vivo cultures of aorta from uremic rats showed high secretion of the Wnt inhibitor sclerostin. In conclusion, the presence of VC lowers BMD, impairs bone metabolism, and affects several pathways in bone. The present results prove the existence of a vasculature to bone tissue cross-talk. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

U2 - 10.1002/jbmr.4203

DO - 10.1002/jbmr.4203

M3 - Journal article

C2 - 33301619

VL - 36

SP - 510

EP - 522

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 3

ER -