Abstract Number: PB0833
Meeting: ISTH 2020 Congress
Background: Bone disease is a significant complication of haemophilia A (HA). However, the pathophysiology is not exactly known and both processes of bone resorption and bone formation could be hypothesized to be altered. It has been suggested that Factor VIII could directly affect bone cells. Moreover, bone cells express protease-activated receptors (PARs) and FVIII deficiency could play a role also by decreasing thrombin production.
Aims: The aim of this study concerned the identification of the specific role played by FVIII, von Willebrand Factor (VWF) and thrombin on osteoclasts and osteoblasts.
Methods: In vitro assays assessed the osteoclastogenic potential of PBMC (Peripheral Blood Mononuclear Cells) isolated from a haemophilic patient. Osteoclastogenesis of healthy donors-PBMC were analysed in the presence of FVIII (2U/ml), VWF (20 µg/ml), FVIII/VWF (2U/ml) with or without osteoprotegerin (OPG 25 ng/ml), and thrombin (Thb 100 nmol/l). Moreover, the effects of these treatments on osteoblast differentiation and activity were also studied.
Results: PBMC from HA patient showed increased ability to form mature osteoclasts compared to those obtained from healthy controls. Moreover, RNA expression analysis performed on patient’s osteoclasts revealed higher levels of RANK, TRAF6, CATHEPSIN K and TCIRG1 genes expression compared to control osteoclasts. VWF appears to play a major role, showing by itself ~45% inhibition of osteoclastogenesis comparable to OPG (the physiologic inhibitor), and even more if is complexed with FVIII (53% inhibition). Thrombin reduces osteoclast differentiation with variable effects (30-50% inhibition).
No alteration of alkaline phosphatase positivity was observed in control osteoblasts treated with Thb and VWF, whereas incubation with FVIII leads to a statistically significant reduction, also revealed in osteoblasts treated with FVIII/VWF.
Conclusions: All these data support that bone loss observed in haemophilic patients could be related to increased osteoclast formation and activity and that coagulation factors directly impact on bone cells.
To cite this abstract in AMA style:Lancellotti S, Battafarano G, Sacco M, Di Gennaro L, De Cristofaro R, Del Fattore A. Bone Remodeling Alterations in Haemophilia: A Cell Biology Approach [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/bone-remodeling-alterations-in-haemophilia-a-cell-biology-approach/. Accessed May 18, 2021.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/bone-remodeling-alterations-in-haemophilia-a-cell-biology-approach/