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Journal of Bone and Mineral Metabolism

, Volume 36, Issue 4, pp 399–409 | Cite as

Bone metabolism markers and angiogenic cytokines as regulators of human hematopoietic stem cell mobilization

  • Pantelis Tsirkinidis
  • Evangelos Terpos
  • Georgios Boutsikas
  • Athanasios Papatheodorou
  • Konstantinos Anargyrou
  • Eleni Lalou
  • Aglaia Dimitrakopoulou
  • Christina Kalpadakis
  • Konstantinos Konstantopoulos
  • Marina Siakantaris
  • Panayiotis Panayiotidis
  • Gerassimos Pangalis
  • Marie-Christine Kyrtsonis
  • Theodoros Vassilakopoulos
  • Maria K. AngelopoulouEmail author
Original Article

Abstract

Hematopoietic stem cell (HSC) mobilization involves cleavage of ligands between HSC and niche components. However, there are scarce data regarding the role of bone cells in human HSC mobilization. We studied biochemical markers of bone metabolism and angiogenic cytokines during HSC mobilization in 46 patients’ sera with lymphoma and multiple myeloma, by ELISA. Significant changes between pre-mobilization and collection samples were found: (1) Bone alkaline phosphatase (BALP) increased, indicating augmentation of bone formation; (2) Receptor activator of Nf-κB ligand/osteoprotegerin ratio (RANKL/OPG) increased, showing osteoclastic differentiation and survival; however, there was no evidence of increased osteoclastic activity; and (3) Angiopoietin-1/Angiopoietin-2 ratio (ANGP-1/ANGP-2) decreased, consistent with vessel destabilization. Poor mobilizers had significantly higher carboxy-terminal telopeptide of collagen type I (CTX) and lower ANGP-1 at pre-mobilization samples, compared to good ones. CTX, amino-terminal telopeptide of collagen type I (NTX) and ANGP-1 pre-mobilization levels correlated significantly with circulating CD34+ peak cell counts. Our results indicate that bone formation and vessel destabilization are the two major events during human HSC mobilization. Osteoblasts seem to be the orchestrating cells, while osteoclasts are stimulated but not fully active. Moreover, ANGP-1, CTX and NTX may serve as predictors of poor mobilization.

Keywords

Bone markers Angiopoietins Hematopoietic stem cells Mobilization Bone cells 

Notes

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interests related to the submitted paper.

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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan KK 2017

Authors and Affiliations

  • Pantelis Tsirkinidis
    • 1
  • Evangelos Terpos
    • 2
  • Georgios Boutsikas
    • 3
  • Athanasios Papatheodorou
    • 4
  • Konstantinos Anargyrou
    • 3
  • Eleni Lalou
    • 5
  • Aglaia Dimitrakopoulou
    • 6
  • Christina Kalpadakis
    • 7
  • Konstantinos Konstantopoulos
    • 5
  • Marina Siakantaris
    • 8
  • Panayiotis Panayiotidis
    • 9
  • Gerassimos Pangalis
    • 10
  • Marie-Christine Kyrtsonis
    • 9
  • Theodoros Vassilakopoulos
    • 5
  • Maria K. Angelopoulou
    • 5
    Email author
  1. 1.Department of Hematology401 General Army Hospital of AthensAthensGreece
  2. 2.Department of Clinical Therapeutics, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  3. 3.Department of Hematology251 General Air Force HospitalAthensGreece
  4. 4.Department of Medical Research251 General Air Force HospitalAthensGreece
  5. 5.Department of Hematology and Bone Marrow Transplantation, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  6. 6.Department of Immunology Research and Flow Cytometry‘Laiko’ General Hospital of AthensAthensGreece
  7. 7.Department of Hematology, School of MedicineUniversity of CreteHerakleionGreece
  8. 8.1st Department of Internal Medicine, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  9. 9.1st Propedeutic Department of Internal Medicine, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  10. 10.Department of Hematology, Psychicon BranchAthens Medical CenterAthensGreece

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