High hydrostatic pressure induces pro-osteoarthritic changes in cartilage precursor cells: A transcriptome analysis

PLOS ONE, Dec 2019

Due to the high water content of cartilage, hydrostatic pressure is likely one of the main physical stimuli sensed by chondrocytes. Whereas, in the physiological range (0 to around 10 MPa), hydrostatic pressure exerts mostly pro-chondrogenic effects in chondrocyte models, excessive pressures have been reported to induce detrimental effects on cartilage, such as increased apoptosis and inflammation, and decreased cartilage marker expression. Though some genes modulated by high pressure have been identified, the effects of high pressure on the global gene expression pattern have still not been investigated. In this study, using microarray technology and real-time PCR validation, we analyzed the transcriptome of ATDC5 chondrocyte progenitors submitted to a continuous pressure of 25 MPa for up to 24 h. Several hundreds of genes were found to be modulated by pressure, including some not previously known to be mechano-sensitive. High pressure markedly increased the expression of stress-related genes, apoptosis-related genes and decreased that of cartilage matrix genes. Furthermore, a large set of genes involved in the progression of osteoarthritis were also induced by high pressure, suggesting that hydrostatic pressure could partly mimic in vitro some of the genetic alterations occurring in osteoarthritis.

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High hydrostatic pressure induces pro-osteoarthritic changes in cartilage precursor cells: A transcriptome analysis

August High hydrostatic pressure induces pro- osteoarthritic changes in cartilage precursor cells: A transcriptome analysis Kevin Montagne 0 1 Yasuko Onuma 1 Yuzuru Ito 1 Yasuhiko Aiki 1 Katsuko S. Furukawa 0 1 Takashi Ushida 0 1 0 Department of Mechanical Engineering, University of Tokyo, Tokyo, Japan, 2 Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology , Tsukuba , Japan , 3 Department of Bioengineering, University of Tokyo , Tokyo , Japan 1 Editor: Mikko Juhani Lammi, University of Umeå , SWEDEN Due to the high water content of cartilage, hydrostatic pressure is likely one of the main physical stimuli sensed by chondrocytes. Whereas, in the physiological range (0 to around 10 MPa), hydrostatic pressure exerts mostly pro-chondrogenic effects in chondrocyte models, excessive pressures have been reported to induce detrimental effects on cartilage, such as increased apoptosis and inflammation, and decreased cartilage marker expression. Though some genes modulated by high pressure have been identified, the effects of high pressure on the global gene expression pattern have still not been investigated. In this study, using microarray technology and real-time PCR validation, we analyzed the transcriptome of ATDC5 chondrocyte progenitors submitted to a continuous pressure of 25 MPa for up to 24 h. Several hundreds of genes were found to be modulated by pressure, including some not previously known to be mechano-sensitive. High pressure markedly increased the expression of stress-related genes, apoptosis-related genes and decreased that of cartilage matrix genes. Furthermore, a large set of genes involved in the progression of osteoarthritis were also induced by high pressure, suggesting that hydrostatic pressure could partly mimic in vitro some of the genetic alterations occurring in osteoarthritis. - Data Availability Statement: All microarray raw and processed data have been submitted to ArrayExpress under the accession number EMTAB-5326. Funding: This study was supported by grants for the Translational Systems Biology and Medicine Initiative (TSBMI) funded by the Japanese Ministry of Education, Culture, Sports, Science and Technology (URL: http://www.mext.go.jp/en/) (KM), the Japan Society for the Promotion of Science (JSPS, URL: https://www.jsps.go.jp/ Introduction During normal physical activity, physiological contact pressures in human articular cartilage vary between 0 and several MPa, reaching around 20 MPa during more intense activities [ 1 ] [ 2 ]. Due to the high water content of cartilage (around 70%), most of the compressive load is sustained by the interstitial fluid [ 3 ], providing cartilage its high stiffness under compression and protecting the collagen-proteoglycan matrix from excessive deformation. As a result, it is assumed that one of the main physical stimuli sensed by chondrocytes embedded in the cartilage matrix is hydrostatic pressure (HP). At the cellular level, moderate HP has been shown to promote cartilage differentiation by increasing the expression of cartilage matrix proteins such as aggrecan and type 2 collagen [4] english/e-grants/) (TU) (grant number 15H01800), the New Energy and Industrial Technology Development Organization (NEDO, URL: http:// www.nedo.go.jp/english/index.html) (KF, YO, YI and YA) and the Japan Agency for Medical Research and Development (AMED, URL: http:// www.amed.go.jp/en/program/) (YO, YI and YA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. [ 5 ], and down-regulating the expression of matrix-degrading enzymes such as MMP-1 through a mechanism involving the transcriptional regulator CITED2 [ 6 ]. In cultured bovine chondrocytes, moderate pressures have no obvious effects on the cytoskeleton [ 7 ] and cyclical pressures even reverse the adverse effects of IL-1β in human chondrocytes [ 8 ]. In vivo, moderate joint loading through physical exercise has been shown to prevent the onset and slow the progression of osteoarthritis [ 9 ]. Conversely, excessive HP has been shown to induce opposing, detrimental effects on cartilage and chondrocytes, with increased apoptosis, decreased extracellular matrix synthesis, increased expression of stress- and inflammation-related genes as well as matrix-degrading enzymes [ 4 ][ 5 ][ 10 ]. High pressure also destabilizes the cytoskeleton [ 7 ] and induces changes in chondrocyte morphology reminiscent of those observed in osteoarthritic cartilage [ 11 ], illustrating the essential role of hydrostatic pressure mechanotransduction in the homeostasis of cartilage. In order to identify genes sensitive to high HP, Sironen et al. performed a cDNA array analysis of chondrocyte cell lines submitted to high HP (30 MPa) for up to 12 h [12]. However, this study focused (...truncated)


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Kevin Montagne, Yasuko Onuma, Yuzuru Ito, Yasuhiko Aiki, Katsuko S. Furukawa, Takashi Ushida. High hydrostatic pressure induces pro-osteoarthritic changes in cartilage precursor cells: A transcriptome analysis, PLOS ONE, 2017, Volume 12, Issue 8, DOI: 10.1371/journal.pone.0183226