Potential anti-osteoporotic activity of low-molecular weight hyaluronan by attenuation of osteoclast cell differentiation and function in vitro.
Due to some severe side effects or lack of efficacy of currently used synthetic drugs, such as bisphosphonates (BPs), the search for new therapeutic agents that can more effectively prevent and treat osteoporosis (OP) has been an increasingly important topic of research. In this study, the low-molecular weight hyaluronan (LMW-HA, 50 kDa) produced by enzymatic degradation of high-molecular weight hyaluronan (HMW-HA, 1922 kDa) from Streptococcus zooepidemicus was evaluated in vitro for its anti-osteoclastogenic potentials using RAW 264.7 murine macrophage cells. LMW-HA (25-200 μg/ml) dose-dependently inhibited the receptor activator of NF-κB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts. Western blot analysis showed that LMW-HA reduced the RANKL-induced expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), gelsolin and c-Src-proline-rich tyrosine kinase 2 suggesting that it could inhibit actin ring formation of osteoclast cells. In addition, LMW-HA inhibited the bone resorption activity of osteoclastic cells by dose-dependently attenuating the RANKL-induced expression of carbonic anhydrase II and integrin β3. RT-PCR analysis showed that LMW-HA dose-dependently decreased the expression of osteoclast-specific genes, such as matrix metalloproteinase 9 (MMP-9) and cathepsin K, suggesting that it has potential to inhibit the differentiation of osteoclastic cells. Taken collectively, these results suggested that LMW-HA (50 kDa) has significant anti-osteoporotic activity in vitro and may be used as a potent functional ingredient in health beneficial foods or as a therapeutic agent to prevent or treat OP.
Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
Chang Won
CW
Lee
Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
Jeong Yeon
JY
Seo
Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
Ji Won
JW
Choi
Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
Jisun
J
Lee
Biostream Technology Co., Yongin-si, Gyeonggi-do 446-930, Republic of Korea.
Joo Woong
JW
Park
Biotopia Co., Ltd., 14, Geodudanji 2-gil, Dongnae-myeon, Chuncheon-si, Gangwon-do 200-883, Republic of Korea.
Jae Yeon
JY
Lee
Biotopia Co., Ltd., 14, Geodudanji 2-gil, Dongnae-myeon, Chuncheon-si, Gangwon-do 200-883, Republic of Korea.
Kyo-Yeol
KY
Hwang
Biotopia Co., Ltd., 14, Geodudanji 2-gil, Dongnae-myeon, Chuncheon-si, Gangwon-do 200-883, Republic of Korea.
Young Shik
YS
Park
Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Republic of Korea. Electronic address: yongil382@catholic.ac.kr.
Yong Il
YI
Park
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D056657:Cathepsin K / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006820:Hyaluronic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D007527:Isoenzymes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008970:Molecular Weight; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy*; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D048029:TNF Receptor-Associated Factor 6 / Q000096:biosynthesis; D000071681:Tartrate-Resistant Acid Phosphatase
D007527:Isoenzymes; D053245:RANK Ligand; D048029:TNF Receptor-Associated Factor 6; D006820:Hyaluronic Acid; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9
Anti-osteoporosis; Low-molecular weight hyaluronan; Osteoclast; RAW 264.7 cells