title: High-molecular-weight hyaluronic acid attenuated matrix metalloproteinase-1 and -3 expression via CD44 in tendinopathy.
abstract: Evidence indicates that hyaluronic acid (HA) mitigates tendinopathy, but the effect of molecular weight is unclear. We investigated the effects of different concentrations and different molecular weights of HA (350 kDa, 1500 kDa, and 3000 kDa) on matrix metalloproteinase (MMP)-1 and -3 expression in IL-1β-stimulated rat tenocytes, and on their dynamic expression in peritendinous effusion from patients with long head of biceps (LHB) tendinopathy after high-molecular-weight (HMW)-HA treatments. Reverse transcription PCR, real-time PCR, and ELISA were used to determine MMP-1 and -3expression. Because CD44 was clearly expressed in the plasma membranes of cultured tenocytes, OX-50, a CD44 antagonist, was used to inhibit CD44 to evaluate the HA mechanism. HA (3000 kDa) significantly (p < 0.001) downregulated the mRNA and protein expression of MMP-1 and -3 in IL-1β-stimulated tenocytes. Its attenuating effects were dose-dependent (p < 0.01). In OX-50-pretreated cells, the mRNA expression of CD44 was not significantly altered, but the mRNA expression of MMP-1 and -3 was significantly upregulated. Visual analogue scale scores were significantly lower, and MMP-1 and -3 expression was significantly (p < 0.05) lower one month posttreatment. HMW-HA attenuated tendinopathy by downregulating MMP-1 and -3 expression. Inhibiting CD44 blocked the effects of HMW-HA.
authors.affiliation: Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.|Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Po-Ting
authors.initials: PT
authors.lastname: Wu
authors.affiliation: Department of Occupational Therapy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Li-Chieh
authors.initials: LC
authors.lastname: Kuo
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.|Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Fong-Chin
authors.initials: FC
authors.lastname: Su
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shih-Yao
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Orthopedics, E-DA Hospital, Kaohsiung, Taiwan.
authors.forename: Tai-I
authors.initials: TI
authors.lastname: Hsu
authors.affiliation: Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Li
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kuen-Jer
authors.initials: KJ
authors.lastname: Tsai
authors.affiliation: Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Orthopedics, E-DA Hospital, Kaohsiung, Taiwan.
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Jou
mesh_terms: D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D052256:Tendinopathy / Q000188:drug therapy / Q000378:metabolism*; D000070916:Tenocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1