Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Reproduction of Characteristics of Extracellular Matrices in Specific Longitudinal Depth Zone Cartilage within Spherical Organoids in Response to Changes in Osmotic Pressure

Version 1 : Received: 17 April 2018 / Approved: 18 April 2018 / Online: 18 April 2018 (08:48:06 CEST)

A peer-reviewed article of this Preprint also exists.

Takada, E.; Mizuno, S. Reproduction of Characteristics of Extracellular Matrices in Specific Longitudinal Depth Zone Cartilage within Spherical Organoids in Response to Changes in Osmotic Pressure. Int. J. Mol. Sci. 2018, 19, 1507. Takada, E.; Mizuno, S. Reproduction of Characteristics of Extracellular Matrices in Specific Longitudinal Depth Zone Cartilage within Spherical Organoids in Response to Changes in Osmotic Pressure. Int. J. Mol. Sci. 2018, 19, 1507.

Abstract

Articular chondrocytes are surrounded by chondroitin sulfate proteoglycan, which attracts an abundant volume of interstitial water. The articular cartilage is compressed with joint-loading and weight-bearing stresses, followed by a bulging of the tissue during times of off-loading. Thus, osmotic pressure in articular cartilage is higher than in other tissues due to the fixed charged density and altered between loading and off-loading due to change in water content. Another unique characteristic of the articular cartilage is that it has longitudinal depth: surface, middle, and deep zones. Since each zone composes unique components of extracellular matrices, each zone has a various level of the osmotic pressure. It was unclear how changes in osmotic pressure affected chondrocyte homeostasis and matrix accumulation in specific longitudinal zone. We hypothesized that change in extrinsic osmotic pressure alters metabolic functions and histogenesis of extracellular matrix by zone-specific chondrocytes. We compared the gene expression of matrix related typical anabolic and catabolic molecules produced by zone specific articular chondrocytes and the immunohistology of these corresponding genes. Since the newly synthesized matrix needed a space to accumulate, we used a chondrocyte-spheroid model formed by longitudinal depth zone-derived cells and altered extrinsic osmotic pressure by changing media containing different osmotic pressures. Anabolic molecules upregulated continuously at high osmotic pressure and transiently by switching back the osmotic pressure from high to low. Each zone derived chondrocytes showed zone specific level of the gene expression. The spheroids once exposed to the high osmotic pressure accumulated extracellular matrices with empty spaces.

Keywords

molecular profile; extracellular matrix; osmotic pressure; depth articular cartilage; spheroidal organoid; cartilage regeneration

Subject

Biology and Life Sciences, Anatomy and Physiology

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