The kidney affects bone development, remodeling and repair by regulating calcium and phosphate homeostasis, producing cytokines and clearing bone regulators. (1) The kidney reabsorbs calcium and phosphate via TRPV6 and NaPi IIa/c. Calcium and phosphate are not only components of bone but also exert direct effects on bone cells via CaSR mediated signaling pathways. (2) The kidney synthesizes 1,25(OH)
2D
3, which can increase calcium and phosphate absorption and reabsorption by stabilizing their transporters. It can also exert direct effects on bone via VDR mediated signaling pathways and increase FGF-23 production in bone. (3) The kidney produces Klotho, which functions as a collaborator with bone-derived FGF-23 to decrease 1,25(OH)
2D
3 or exerts direct effects on bone independently. (4) The kidney produces BMP-7, which can exert direct effects on bone by activating Smad1/4/5/8 or TAK1/MKK/p38 signaling pathways. (5) The kidney synthesizes EPO, which has both direct effects on bone by activating JAK2, mTOR and PI3K signaling pathways and indirect effects through bone marrow. (6) OPG and sclerostin are bone-derived bone regulators. They are mainly cleared in the kidney. (7) PTH mediates the crosstalk between the kidney and bone. There are several feedback loops between PTH and serum calcium, 1,25(OH)
2D
3 and FGF-23.
: produce or promote,
: inhibit,
(
red arrow) represents the effects of kidney,
(
yellow
arrow) represents the effects of bone,
(
black arrow) represents the effects of others,
(
pink box with up arrow) represents up-regulation or promotion,
(
blue box with down arrow) represents down-regulation or inhibition, 1α(OH)ase: 1α-hydroxylase, ADAMTMS: a disintegrin and metalloproteinase with thrombospondin motifs, ALP: alkaline phosphatase, BMP: bone morphogenetic protein, Ca
2+: calcium, CaSR: calcium-sensitive receptor, ECM: extracellular matrix, FGF: fibroblast growth factor, HSC: hematopoietic stem cell, MMP: metalloproteinase, MSC: mesenchymal stem cell, OBL: osteoblast, OCL: osteoclast, OPG: osteoprotegerin, PO
4: phosphate, PTH: parathyroid hormone, RANKL: receptor activator of nuclear factor NF-κβ ligand, Runx2: runt-related gene 2, VDR: vitamin D receptor, VEGF: vascular endothelial growth factor