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Mari Huttu

Cell-tissue interactions in normal, aging and osteoarthritic articular cartilage


Professor Juha Tuukkanen, University of Oulu, Finland


Adjunct Professor Holly Leddy, Duke University, United States of America

Associate Professor Susanna Miettinen, University of Tampere


Professor Rami Korhonen, University of Eastern Finland, Finland

Professor Mikko Lammi, University of Umeå, Sweden

Articles of the thesis

Abstract of the thesis

Articular cartilage is white, smooth, almost frictionless tissue without nerves or blood vessels covering ends of the long bones. It consists of one type of cells, chondrocytes, and extracellular matrix (ECM) comprising mainly tissue fluid, collagens and proteoglycans (PGs). The role of chondrocytes is to maintain the ECM.

     Osteoarthritis (OA) is the most common joint disease in the world causing joint pain and decreased mobility of the joint. Age, gender, genetics, nutrition, obesity and abnormal joint loading are examples of risk factors of OA. Many early changes or symptoms, such as reduction of PG and disorganization of collagen fibrils, associated with OA are similar to changes in normal aging. On the other hand, aging also affects chondrocyte metabolism, and results in advanced glycation end products (AGEs) congregating the ECM. AGEs increase collagen cross-linking and ECM stiffness. Knowledge of the pathology OA and its progress is fairly well understood. However, at the cell and tissue level, many features are still unclear. For example, which structural components and biomechanical properties of articular cartilage correlate together and participate in regulation of cell shape and volume in OA, are still unknown. It is also not known, how aging or induced collagen cross-linking affects the chondrocyte responses.

     In this thesis, celltissue interactions in normal, aging and osteoarthritic articular cartilage were investigated. Chondrocytes were imaged by confocal laser scanning microscopy (CLSM) after osmotic or mechanical loading or without any loading to determine chondrocyte volume and shape. Reference techniques, such as biomechanical testing, polarized light microscopy (PLM), digital densitometry (DD), Fourier transform infrared microspectroscopy (FTIR) and high-performance liquid chromatography (HPLC), were utilized to define the function, structure and composition of samples. The samples were collected from normal healthy bovine lateral patellar groove (LPG) of the femur, bovine lateral aspect of the distal pole of 8 patellae and osteoarthritic human femoral heads. Half of the patellae samples were then ribose-treated for collagen cross-linking to simulate aging.

     Superficial chondrocyte volume increase and volume recovery after hypo-osmotic challenge were observed not to be reliant on contents of immersion media or temperature. Chondrocyte volumes, in all media and temperature groups, first increased after hypotonic loading and then recovered back to control levels. Simulated aging by in vitro glycation, was perceived to decrease chondrocyte deformation in the upper zone of articular cartilage during mechanical loading. Mechanical forces were found to affect the deeper zone of articular cartilage by increasing chondrocyte deformation processes. In OA, the collagen fibril orientation and organization were found to be the most important ECM structural components to regulate chondrocyte volume in the superficial layer of articular cartilage. Depth-wise chondrocyte shape might be regulated more by PGs and collagen fibrils together. Alterations in collagen fibril orientation, organization and PGs and celltissue interactions in osteoarthritic tissue possibly affect the chondrocyte biosynthesis.

     In conclusion, chondrocyte volume alterations after hypo-osmotic challenge are not dependent on immersion media or temperature. This is methodologically very important detail and underlines the significance of chondrocyte environment by comparing laboratory measurements to the real life. In simulated aging, alterations in the biomechanical responses of chondrocytes differ according to the zone of the articular cartilage. It is a noteworthy and important finding, how AGEs, one of the signs of aging in articular cartilage, affect the chondrocyte deformation processes divergently in the upper and the deeper zones of articular cartilage. Collagen fiber orientation angle chiefly regulate chondrocyte volume and depth-wise shape in osteoarthritic human hip cartilage. The results deepen the knowledge of osteoarthritic changes in cells and tissue in human cartilage.

  1. Huttu M, Turunen S, Sokolinski V, Tiitu V, Lammi M, Korhonen RK: Effects of medium and temperature on cellular responses in the superficial zone of hypo-osmotically challenged articular cartilage. J Function Biomater 3(3): 544-555, 2012 [Pubmed] [Full text]

  2. Fick JM, Huttu MR, Lammi MJ, Korhonen RK: In vitro glycation of articular cartilage alters the biomechanical response of chondrocytes in a depth-dependent manner. Osteoarthritis Cartilage 22(10): 1410-1418, 2014 [Pubmed] [Full text]

  3. Huttu MR, Puhakka J, Mäkelä JT, Takakubo Y, Tiitu V, Saarakkala S, Konttinen YT, Kiviranta I,Korhonen RK: Cell-tissue interactions in osteoarthritic human hip joint articular cartilage. Connect Tissue Res 55(4): 282-291, 2014 [Pubmed] [Full text]

Last updated January 29, 2019

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