The function and meaning of receptor activator of NF-κB ligand in arterial calcification.
Osteoclast-like cells are known to inhibit arterial calcification. Receptor activator of NF-κB ligand (RANKL) is likely to act as an inducer of osteoclast-like cell differentiation. However, several studies have shown that RANKL promotes arterial calcification rather than inhibiting arterial calcification. The present study was conducted in order to investigate and elucidate this paradox. Firstly, RANKL was added into the media, and the monocyte precursor cells were cultured. Morphological observation and Tartrate resistant acid phosphatase (TRAP) staining were used to assess whether RANKL could induce the monocyte precursor cells to differentiate into osteoclast-like cells. During arterial calcification, in vivo and in vitro expression of RANKL and its inhibitor, osteoprotegerin (OPG), was detected by real-time PCR. The extent of osteoclast-like cell differentiation was also assessed. It was found RANKL could induce osteoclast-like cell differentiation. There was no in vivo or in vitro expression of osteoclast-like cells in the early stage of calcification. At that time, the ratio of RANKL to OPG was very low. In the late stage of calcification, a small amount of osteoclast-like cell expression coincided with a relatively high ratio of RANKL to OPG. According to the results, the ratio of RANKL to OPG was very low during most of the arterial calcification period. This made it possible for OPG to completely inhibit RANKL-induced osteoclast-like cell differentiation. This likely explains why RANKL had the ability to induce osteoclast-like cell differentiation but acted as a promoter of calcification instead.
Department of Geriatrics, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
Bin
B
Nie
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Shao-Qiong
SQ
Zhou
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Xin
X
Fang
Department of Geriatrics, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China. wyzsy@163.com.
Shao-Ying
SY
Zhang
Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. smguan16@yahoo.com.
Si-Ming
SM
Guan
D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000235:genetics* / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase; D061205:Vascular Calcification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
arterial calcification; osteoclast-like cells; osteoprotegerin; receptor activator of NF-κB ligand