D1 :Collagen lecture Flashcards
what is the definition of connective tissue?
defined as any supporting tissue that lies between other tissues and consists of cells embedded in a relatively large amount of extracellular matrix. Includes, bone cartilage and loose connective tissue
where does connective tissue come from?
- Mesodermal origin (can be ectomesenchyme-only for head and neck)
- loosely packed
- unspecialized cells
- gelatinous ground substance
- from which connective tissue, bone cartilage and the circulatory and lymphatic systems develop
what is connective tissue?
- Few cells within it, mainly fibroblasts
- Made up of an extracellular matrix
- Fibrous polymers mainly collagens
- Framework of vertebrate body
- Major component cartilage and bone
- Minor component brain and spinal cord
what cells are found in connective tissue?
cells of mesenchyme
what is the definition of fibroblast?
A common cell type found in connective tissue. Fibroblasts secrete an extracellular matrix rich in collagen and other extracellular matrix macromolecules. Migrates and proliferates readily in wounded tissue and in tissue culture
what is the structure of fibroblasts?
- Microtubules
- Filaments
- Junctions
- Heterogeneity
- Ageing
- Contraction and Motility
Name some fibroblasts.
actin, tubules and the intermediate filament (vimentin)
Describe fibroblast heterogeneity.
- Cell size
- Cell Shape
- Proliferative activity
- Motility and attachment
- Collagen and Extracellular Matrix proteins
- Actin Isoforms
why might fibroblasts be termed as stem cells?
differentiate into :
- bone cell (osteoblast/osteocyte)
- fat cell (adipocyte)
- cartilage cell (chondrocyte)
- smooth muscle cell
what are the fibres around a fibroblast called?
cologen
what is the definition of extracellular matrix?
defined as- a complex network of polysaccharides (such as glycosaminoglycans or cellulose) and proteins (such as collagen) secreted by cells. Serves as a structural element in the tissues and also influences their development and physiology
what is extracellular matrix function?
• Support for cells. • Pattern of ECM regulates a) Polarity b) Cell division, c) adhesion d) motility. • Development a) migration b) differentiation. • Growth Factors
Name some different shapes and sizes of ECM molecules.
- fibronectin
- fibrillar collagen
- laminin
- tenascin
- hyaluronan
- decorin
what makes up extracellular matrix?
- Not solely made up of cells
- Intricate network of macromolecules
- Secreted by cells locally
- Assembled and organised into meshwork by cells producing them
what do varieties of extracellular matrix form?
bone, teeth, cornea and tendons
what is the extracellular matrix not and why?
-Not inert scaffold
• Active and complex role in regulating cell behaviour
• Influences: Cell survival, development, migration, proliferation, shape and function
what is the connective tissue of oral tissues?
- Mainly extracellular matrix
- Matrix made up of proteins,
- proteoglycans,glycoproteins and GAGs
- Main protein: collagens
- Main proteoglycans: decorin,
- fibromodulin and lumican, CD44
- Main GAG: hyaluronan
- Main cell: fibroblast
what are glycoaminoglycans (GAGs)?
• Repeating disaccharide chains • Amino sugar (N-acetylglucosamine or N- acetylgalactosamine • Uronic acid (glucuronic or iduronic) • Highly negatively charged- sulphate or carboxyl
what is hyaluronan (HA)?
non-sulphated glycosaminoglycan (main one in oral cavity)
what is the structure of hyaluronan?
- Disaccharide repeating units of N- acetylglucosamine linked with glucuronic acid.
- Molecular weight 20000Da and 2000000Da
how is hyaluronan synthesised?
through the cell membrane
what are the functions of hyaloronan?
• Has ability to bind water molecules-
cosmetic industry
• Highly viscoelastic- treatment in osteoarthritis.
• Increased tumours and elevated at certain stages of wound healing.
• Linked increased fibroblast migration effect size dependent
Give an overview of collagen. (remember this)
- Fibrous proteins
- Most abundant in mammals
- Primary feature long, stiff triple stranded helical structure
- At least 25 types of collagen (more likely 50)
- 80-90% of all collagen Type I, II and III.
what is the structure of collagen?
- Collagen I: 330nm long and thin 1.5nm
- Structural Unit is a triple helix
- Three coiled subunits 1050 amino acids (closely intertwined so can’t break down by enzymes -very strong)
describe how cologne structure comes about.
- glycine:small (smallest AA because you want it tightly intertwined)
- proline:fixed angle allows helix formation
- hydroxyproline : fixed angle allows helix formation (no RNA gene with these AA so synthesised by the cell)
- hydroxylysine: stabilises side by side packing (same as above)
Name the different types of collagen.
- fibril-forming collagens (type I,II,III,V and XI)
- network-forming collagens (types IV, VIII and X)
- Fibril-associated collagens with interrupted triple helices (Type IX,XII,XIV,XVI and XIX)
- Transmembrane collagens (types XIII and XVII)
- other types of collagen
how does it know where to start forming the coil (collagen biosynthesis) ?
Enzymes involved:
H glycosylation enzymes Protein disulphide
isomerase
what signals the correct alignment?
15 amino acids which are non conserved in C pre-pro region
Name one use of collagen in dentistry.
collagen gum grafting
what are some diseases caused by collagen excess?
- Scleroderma- rare chronic disease characterized by excessive deposits of collagen- growth factors
- Oral submucosa fibrosis: chronic debilitating and precancerous caused by chewing habit- increase in type III and then type I collagen.
what are some diseases caused by insufficient collagen?
- osteogenesis imperfecta
- Ehlers-danlos sydrome
- collagenopathy
what cause osteogenesis imperfecta?
- brittle bones
- Type 1- normal quality insufficient quantity A and B are when have dentinogenesis imperfecta (opalescent teeth).
- Type 4 A and B quantity sufficient but not high enough quality
what causes Ehlers-danlos syndrome?
-rare genetic disorder caused by defect in collagen synthesis
• Symptoms unstable, flexible joints- skin and tendons easily stretched.
• Mutations in ADAMTS2, Col1A1, Col1A2, Col3A1, Col5A1, Col 5A2, PLOD1 and TNXB
what are symptoms of collagenopathy, type II and XI?
-poor bone development, problems with
hearing, sight, cleft plate, small lower jaw.
• Mutations: Col 11A1, Col 11A2 and Col 2A1.
Name and Describe a disease associated with collagen in diet?
- Scurvy: a deficiency disease lack of vitamin C- needed for hydroxylation proline to hydroxyproline.
- If not present- form too few hydrogen bonds in collagen.
- Skin, bone teeth weakness and malformation.
- Blood vessels weakened-bleeding
Name other matrix factors.
- Fibronectin- glycoprotein, cryptic bioactivities.
- Laminin- glycoprotein, cryptic bioactivities.
- Growth factors- affect cell behaviour.
- Integrins and signalling.
- CD44
