The roles of extracellular matrix molecules matrilins and aggrecan in bone development and articular cartilage functions

Li, Ping (2020): The roles of extracellular matrix molecules matrilins and aggrecan in bone development and articular cartilage functions. Dissertation, LMU München: Medizinische Fakultät

Abstract

Bones are important constituents of the organ systems of the vertebrates providing body support, physical protection for inner organs, movement facilitation, mineral storage and a niche for hematopoiesis [1, 2]. In human, there are more than 200 bones, which derive through two developmental pathways: 1) flat bones of the skull form directly from the condensation of the skeletogenic mesenchymal cells in the process of intramembranous ossification (IO); 2) while long bones of the appendicular and axial skeleton arise through a cartilaginous intermediates in the process of endochondral ossification (EO) [3]. EO starts with the condensation of the skeletogenic mesenchymal cells at the sites of the future bones, and the progenitor cells in these aggregates, under the guidance of various factors, differentiate into chondrocytes forming the cartilage template. Chondrocytes within the cartilage anlage begin to proliferate and synthesize cartilage-specific extracellular matrix, which is rich in collagen II and aggrecan [3]. The cartilage templates subsequently undergo maturation, hypertrophy, vascular invasion and mineralization, and the bones grow both laterally and longitudinally [4, 5]. As a result of the morphogenetic processes, embryonic cartilage is largely replaced by bone (transient cartilage), except the ends of long bones where it remains intact and forms the permanent articular cartilage [6, 7]. Articular cartilage (AC) is a highly hydrated, strong, resilient, avascular, alymphatic and aneural tissue. Covering the ends of long bones, AC is not only providing a lubricating, frictionless surface for the synovial, diarthrodial joints, but is also essential to distribute the mechanical loading generated during movement [8]. AC is composed of a relatively small number of chondrocytes, which lay down a specialized extracellular matrix (ECM). The major constituents of the ECM are the organic components (about 40%) and water (about 60%) [9, 10]. AC is characterized by a unique zonal structure with varying structural and biochemical properties. Generally, the AC is divided into four vertical layers: the superficial zone, the middle zone, the deep zone and the calcified cartilage zones[11]. All these zones have characteristic mechanical behavior for loading stimuli [12]. The ECM of both the transient and permanent cartilage provides physical support for chondrocytes, and acts as a sponge reserving growth factors and other cytokines, which in turn could modulate cell proliferation and differentiation. The ECM is predominantly composed of fibrillary collagens, proteoglycans, and non-collagenous molecules [6, 13, 14]. These constituents interact with each other forming a unique protein network, which maintain the biochemical and biomechanical characters of the cartilage. The collagen fibrils provide tensile strength, whereas proteoglycans are responsible for the osmotic swelling and the elastic properties of the tissue [13, 15]. The cartilage ECM is a dynamic network, which undergoes modeling and remodeling along the whole life. Homeostasis of cartilage is maintained by complex mechanisms controlling the turnover of the ECM by regulating the balance between anabolic and catabolic processes [16]. Mutations in matrix proteins resulting in abnormal organization of the ECM could eventually affect the development of endochondral bones and the function of articular cartilage [17, 18]. Abnormal development and growth of the transient cartilage lead to various chondrodysplasias; while degenerative diseases, such as osteoarthritis, are characteristic for the permanent AC [19].

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Bone development, Articular cartilage, Matrilins, Aggrecan, Chondrodysplasia, Osteoarthritis
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 14. September 2020
• 1. Bericht­erstatter:in: Aszódi, Attila