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Int. J. Mol. Sci. 2016, 17(4), 613; doi:10.3390/ijms17040613

Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity

1,2,3,4
,
5
,
1,2,3,4
,
1,2,3,4
and
1,2,3,4,*
1
Renal Division, Peking University First Hospital, No. 8 Xishiku Street, Xi Cheng District, Beijing 100034, China
2
Peking University Institute of Nephrology, Beijing 100034, China
3
Key Laboratory of Renal Disease, Ministry of Health, Beijing 100034, China
4
Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing 100034, China
5
Department of Cardiology, Peking University First Hospital, No. 8 Xishiku Street, Xi Cheng District, Beijing 100034, China
*
Author to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 24 February 2016 / Revised: 19 April 2016 / Accepted: 20 April 2016 / Published: 22 April 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [3468 KB, uploaded 22 April 2016]   |  

Abstract

Heparin has been proven to enhance bone resorption and induce bone loss. Since osteoclasts play a pivotal role in bone resorption, the effect of heparin on osteoclastogenesis needs to be clarified. Since osteocytes are the key modulator during osteoclastogenesis, we evaluated heparin’s effect on osteoclastogenesis in vitro by co-culturing an osteocyte cell line (MLO-Y4) and pre-osteoclasts (RAW264.7). In this co-culture system, heparin enhanced osteoclastogenesis and osteoclastic bone resorption while having no influence on the production of RANKL (receptor activator of NFκB ligand), M-CSF (macrophage colony-stimulating factor), and OPG (osteoprotegerin), which are three main regulatory factors derived from osteocytes. According to previous studies, heparin could bind specifically to OPG and inhibit its activity, so we hypothesized that this might be a possible mechanism of heparin activity. To test this hypothesis, osteoclastogenesis was induced using recombinant RANKL or MLO-Y4 supernatant. We found that heparin has no effect on RANKL-induced osteoclastogenesis (contains no OPG). However, after incubation with OPG, the capacity of MLO-Y4 supernatant for supporting osteoclast formation was increased. This effect disappeared after OPG was neutralized and reappeared after OPG was replenished. These results strongly suggest that heparin promotes osteocyte-modulated osteoclastogenesis in vitro, at least partially, through inhibiting OPG activity. View Full-Text
Keywords: unfractionated heparin; osteocyte; osteoclast; osteoclastogenesis; osteoprotegerin (OPG) unfractionated heparin; osteocyte; osteoclast; osteoclastogenesis; osteoprotegerin (OPG)
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Li, B.; Lu, D.; Chen, Y.; Zhao, M.; Zuo, L. Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity. Int. J. Mol. Sci. 2016, 17, 613.

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