title: Applying an excessive mechanical stress alters the effect of subchondral osteoblasts on chondrocytes in a co-culture system.
abstract: Osteoarthritis (OA) sometimes occurs as a consequence of repeated microtrauma involved in parafunction, which may lead to microfracture in the subchondral bone. The aim of this in vitro study was to evaluate the effects of subchondral osteoblasts in loading with repeated excessive mechanical stress on the metabolism of overlying chondrocytes. A high-magnitude cyclic tensile stress of 15 kPa (30 cycles min(-1)) was applied to the cultured osteoblasts obtained from porcine mandibular condyles. The chondrocytes in alginate beads were then co-cultured with mechanically stressed or unstressed osteoblasts. Chondrocytes co-cultured with unstressed osteoblasts showed a phenotypic shift to hypertrophic chondrocytes, characterized by decreased expression of type II collagen, aggrecan, Sry-related HMG box (SOX-9), and cartilage oligomeric matrix protein (COMP) genes and increased expression of type X collagen and bone sialoprotein (BSP) genes, suggesting that the co-culture may change the chondrocyte differentiation to some extent. These changes were more distinct in chondrocytes co-cultured with excessively mechanically stressed osteoblasts. After co-culture with stressed osteoblasts, the expressions of matrix metalloproteinase (MMP)1, MMP3 and MMP13 genes were also enhanced and the synthesis of DNA, proteoglycan and collagen were significantly decreased in chondrocytes. These results demonstrate that alterations in cartilage metabolism can be induced by stressed osteoblasts, indicating a possible explanation for the onset and progression of OA.
authors.affiliation: Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan.
authors.forename: Yu-Yu
authors.initials: YY
authors.lastname: Lin
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Satoru
authors.initials: S
authors.lastname: Ohkuma
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwabuchi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tanne
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamiya
authors.forename: Ryo
authors.initials: R
authors.lastname: Kunimatsu
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Huang
authors.forename: Motoko
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Mitsuyoshi
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
mesh_terms: D053674:Aggrecans / Q000032:analysis; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D018920:Coculture Techniques; D003094:Collagen / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis; D024121:Collagen Type X / Q000032:analysis; D004247:DNA / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006984:Hypertrophy; D058574:Integrin-Binding Sialoprotein; D008335:Mandibular Condyle / Q000166:cytology; D064235:Matrilin Proteins; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D010006:Osteoblasts / Q000502:physiology*; D010641:Phenotype; D011509:Proteoglycans / Q000032:analysis; D055758:SOX9 Transcription Factor / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis; D013314:Stress, Mechanical; D013552:Swine; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D024121:Collagen Type X; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D058574:Integrin-Binding Sialoprotein; D064235:Matrilin Proteins; D011509:Proteoglycans; D055758:SOX9 Transcription Factor; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D003094:Collagen; D004247:DNA; D000469:Alkaline Phosphatase; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1