week 5 - musculoskeletal system Flashcards
two main types of ECM
interstitial connective tissue matrix and the basement membrane
what is the ECM
a complex network of proteins and polysaccharides that provides structural, adhesive and biochemical signalling support
where is the ECM
- Dermal layer of skin
- Bone
- Tendon
- Cartilage
- Blood vessel walls
- Vitreous body of the eye
- Cornea
- Basement membrane
functions of ECM
Anchors cells (through cell-ECM junctions)
Strongly influences embryonic development
Provides pathways for cellular migration (eg. wound repair)
Binds to growth factors – either concentrating them locally or removing them or sequestering them
Provides a residence for roaming phagocytic cells
Establishes and maintains stem cell niches
provides mechanical and structural support for most tissues
five classes of macromolecules found in acellular component of a tissue
collagens, elastin, proteoglycans, hyaluronan (glycosaminoglycan) and glycoproteins
main function of collagen
to provide tensile strength
types of collagen
fibrillar and sheet/network forming
structure of collagen
3 collagen peptides form a triple helix
where are collagens 1-5 found
type I - dermis, tendons, ligaments, bones, fibrocartilage
II - hyaline cartilage
III - liver, bone marrow, lymphoid organs, granulation tissue
IV - basement membranes
V - linker to basement membrane, cornea
function of sheet/network forming collagen
provides support/filter - allows movement across BM
fibres found in ECM
collagen and elastin
structure of elastin
structural protein arranged as fibres
assembly into these fibres requires the presence of a structural protein called fibrillar which gets incorporated into the elastin fibres
when are collagen fibres uni-directionally aligned
when more strength is required eg. in tendons and ligaments - gives more resistance to mechanical load
what is ground substance
made of proteoglycans, glycosaminoglycans (GAGs) and glycoproteins
fills spaces between fibres and cells
amorphous, gel-like, non-fibrous substance surrounding cells
what are proteoglycans
GAGs (carbohydrate component) linked with a core protein
main function of a proteoglycan
highly negatively charged and so attract water - water retention and swelling property provides resistance to compressive forces
some can form aggregates
examples of GAGs and where they are found
hyaluronic acid - synovial fluid
chondroitin sulphate - cartilage
keratan sulphate - cartilage
heparan sulphate - BM
examples of proteoglycans and their location
aggrecan - cartilage
perlecan - BM
syndecan - cartilage
decorin - widespread in connective tissues
describe aggrecan
its a multimolecular aggregate and is an important part of cartilage
assembles along a hyaluronic acid core to form a negatively charged aggregate
Interacts with type two collagen and together they resist tensile force but also provides resistance to deformation
difference between proteoglycans, GAGs and glycoproteins
proteoglycans are a subclass of glycoproteins GAGs form proteoglycans when linked with a core protein
glycoproteins found in ground substance and their functions
fibrillin controls deposition and orientation of elastin
fibronectin - linker role in BM, organises ECM and participates in cell attachment to BM
laminin is the primary organiser of BM layer - also interacts with the integrins that are present in the hemidesmosome and therefore has a role in maintaining the integrity of the dermo-epidermal junction
how are most ECM components synthesised
fibroblasts produce most ECM components
Fibroblasts secrete the fibrous proteins –> post translational modification -> assembled into fibres
synthesis of proteoglycans
fibroblasts produce the core protein of the proteoglycan - firstly in rER then there is the addition fo polysaccharide as disaccharide in Golgi
delivered to extracellular compartment by exocytosis and then is assembled with other ECM components
describe collagen synthesis
synthesised as procollagen
post translational modifications are glycosylation and hydroxylation
protein assembly in the form of a triple helix
elastin synthesis
synthesised as tropoelastin
post translational modification is hydroxylation and then the proteins are assembled as a fibrillin scaffold and cross-linked fibres
when does tissue fibrosis occur
it is the result of abnormal responses to organ injury and results from the hyperproliferation of fibroblasts and excessive ECM synthesis
degradation of ECM by pathogens
some pathogens secrete collagenases that breakdown the ECM and provide access to the body so bacteria can then invade
how does the ECM act in epithelial tissue
can lie underneath epithelia and endothelia
Can surround cells such as muscle fibres
Can separate two sheets of cells
Provides structural support for the epithelia of skin as well as a layer for selective permeablility
components of BM in epithelial tissue
collagen 4, laminin, perlecan and nidogen
functions of BM in epithelial tissue
support, binding to underlying connective tissue, mediates signals between cells and connective tissue, determines cell polarity, permits flow of nutrients, path for cell migration and is a barrier to downward growth
how does a disorder of BM lead to cancer
epithelial tumours are regarded as malignant once BM has been breached
describe some disorders of the BM
epidermolysis bullosa - attachment of epidermis to BM
goodpastures syndrome - autoantibodies to collagen IV destroy BM in glomerulus and lung
diabetes mellitus - thickening of BM in glomerulus changes permeability
where is specialised connective tissue located
bone cartilage adipose tissue (fat) blood bone marrow, lymphoid tissue
what is the ECM in bone called
osteoid
what are the cellular components of bone and their functions
Osteoblasts – matrix production (bone equivalent of fibroblasts) - make new bone cells and secrete collagen
Osteocytes – found in mature bone and were once osteoblasts but have now become surrounded and entrapped in their own matrix – regulate mineral homeostasis
Osteoclasts – involves in bone degradation or resorption – derived from monocyte-macrophage precursor – has multiple large nuclei and a ruffle border that releases powerful degradative acid and enzymes
acellular components of bone
organic component makes up 30% - type I collagen and osteocalcin inorganic component (70%) - hydroxyapatite
what synthesises cartilage
chondrocytes
components of cartilage
formed from type II collagen - cartilage also contains chondroitin sulphate, keratan sulphate, hyaluronic acid and aggrecan
types of cartilage
hyaline
elastic
fibrocartilage
what do the negative charges associated with aggrecan mean
means cartilage can attract water molecules
features of hyaline cartilage
few visible collagen fibres
avascular
has perichondrium - except articular cartilage
features of fibrocartilage
abundant collagen fibres
avascular
no perichondrium
features of elastic cartilage
contains elastic fibres
avascular
has perichondrium
location of hyaline cartilage
nasal septum, larynx, tracheal rings, articular surfaces, sternal ends of ribs, epiphyseal growth plate
location of fibrocartilage
IV discs, sternoclavicular joint, pubic symphysis
location of elastic cartilage
external ear, epiglottis, auditory tube