Primary hyperparathyroidism is associated with increased circulating bone marrow-derived progenitor cells.
Recently, parathyroid hormone (PTH) was shown to support survival of progenitor cells in bone marrow. The release of progenitor cells occurs in physiological and pathological conditions and was shown to contribute to neovascularization in tumors and ischemic tissues. In the present study we sought to investigate prospectively the effect of primary hyperparathyroidism (PHPT) on mobilization of bone marrow-derived progenitor cells. In 22 patients with PHPT and 10 controls, defined subpopulations of circulating bone marrow-derived progenitor cells (BMCs) were analyzed by flow cytometry (CD45(+)/CD34(+)/CD31(+) cells indicating endothelial progenitor cells, CD45(+)/CD34(+)/c-kit(+) cells indicating hematopoietic stem cells, and CD45(+)/CD34(+)/CXCR4(+) cells indicating progenitor cells with the homing receptor CXCR4). Cytokine serum levels (SCF, SDF-1, VEGF, EPO, and G-CSF) were assessed using ELISA. Levels of PTH and thyroid hormone as well as serum electrolytes, renal and liver parameters, and blood count were analyzed. Our data show for the first time a significant increase of circulating BMCs and an upregulation of SDF-1 and VEGF serum levels in patients with PHPT. The number of circulating BMCs returned to control levels measured 16.7 +/- 2.3 mo after surgery. There was a positive correlation of PTH levels with the number of CD45(+)/CD34(+)/CD31(+), CD45(+)/CD34(+)/c-kit(+), and CD45(+)/CD34(+)/CXCR4(+) cells. However, there was no correlation between cytokine serum concentrations (SDF-1, VEGF) and circulating BMCs. Serum levels of G-CSF, EPO, and SCF known to mobilize BMCs were even decreased or remained unchanged, suggesting a direct effect of PTH on stem cell mobilization. Our data suggest a new function of PTH mobilizing BMCs into peripheral blood.
Brunner
Stefan
S
Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany.
Theiss
Hans Diogenes
HD
Murr
Alfons
A
Negele
Thomas
T
Franz
Wolfgang-Michael
WM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D001773:Blood Cells / Q000737:chemistry / Q000473:pathology*; D001854:Bone Marrow Cells / Q000737:chemistry / Q000473:pathology*; D002118:Calcium / Q000097:blood; D002452:Cell Count; D054377:Chemokine CXCL12 / Q000097:blood; D004921:Erythropoietin / Q000097:blood; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000097:blood / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D013234:Stem Cells / Q000737:chemistry / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D018952:Antigens, CD34; D054377:Chemokine CXCL12; D010281:Parathyroid Hormone; D010710:Phosphates; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D002118:Calcium