Lithium and Copper Induce the Osteogenesis-Angiogenesis Coupling of Bone Marrow Mesenchymal Stem Cells via Crosstalk between Canonical Wnt and HIF-1<i>α</i> Signaling Pathways

<div>Lithium and copper costimulation can promote osteogenesis and angiogenesis via crosstalking between the canonical Wnt and HIF-1<i>α</i> signaling pathways. (a) The BMSCs were exposed to 25 <i>μ</i>M copper, 500 <i>μ</i>M lithium, and costimulation. The Alizarin Red staining was performed to investigate the calcium nodules after four weeks of stimulation. The immunofluorescence (IF) staining was used to detect the VEGF expression in the BMSCs after 7 days of coculture. (b, c) The osteogenesis (ALP, osterix) and angiogenesis (VEGF) genes were detected by RT-qPCR and western blot in the BMSCs under 25 <i>μ</i>M Cu<sup>2+</sup>, 500 <i>μ</i>M Li<sup>+</sup>, and costimulation intervention for 7 days. (d, e) ChIP analysis for HIF-1<i>α</i>, <i>β</i>-catenin, osterix, and VEGF promoter binding site following stimulation with 25 <i>μ</i>M copper and 500 <i>μ</i>M lithium or costimulation for 7 days. <svg height="8.32035pt" id="M43" style="vertical-align:-0.2063999pt" version="1.1" viewbox="-0.0498162 -8.11395 27.8368 8.32035" width="27.8368pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g></svg> holes per group. Data shown are of a single representative experiment with an experiment repeated two times with three technical replicates in each experiment. 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Stem Cells International

fig6

Figure 6

Figure 6: Lithium and Copper Induce the Osteogenesis-Angiogenesis Coupling of Bone Marrow Mesenchymal Stem Cells via Crosstalk between Canonical Wnt and HIF-1<i>α</i> Signaling Pathways 

Figure 6 | Lithium and Copper Induce the Osteogenesis-Angiogenesis Coupling of Bone Marrow Mesenchymal Stem Cells via Crosstalk between Canonical Wnt and HIF-1α Signaling Pathways 

stemells国际

液态和铜素生成-人工生成博尔马鲁米申奇马尔电磁槽通过康宁世界与HIF-1交叉聊天α信号路径

图6