title: Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis.
abstract: Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.
authors.affiliation: Department of Orthopaedic Surgery, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589-8511, Japan. makagi@med.kindai.ac.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Akagi
authors.forename: Shunji
authors.initials: S
authors.lastname: Nishimura
authors.forename: Kohji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Takumi
authors.initials: T
authors.lastname: Kakinuma
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Munakata
authors.forename: Chiaki
authors.initials: C
authors.lastname: Hamanishi
mesh_terms: D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism / Q000503:physiopathology; D011509:Proteoglycans / Q000096:biosynthesis; D051131:Receptors, Oxidized LDL / Q000235:genetics / Q000378:metabolism*; D013718:Tensile Strength / Q000502:physiology*
chemical_list: D008077:Lipoproteins, LDL; D011509:Proteoglycans; D051131:Receptors, Oxidized LDL; C099252:oxidized low density lipoprotein