Cells of Connective Tissue PDF

Cells of connective tissue By the end of this lecture you should be able to; Classify cartilage into its various types; (a) HYALINE (articular) CARTILAGE (b) FIBROCARTILAGE (c) ELASTIC CARTI...

Cells of connective tissue By the end of this lecture you should be able to; Classify cartilage into its various types; (a) HYALINE (articular) CARTILAGE (b) FIBROCARTILAGE (c) ELASTIC CARTILAGE and give examples where each is found, and state their functions. Describe the gross, histological and cellular features of these cartilages. Recognise the importance of physiological mechanical load in maintaining the health of connective tissues and the concept of ‘Form Follows Function’. Understand how hyaline cartilage is adapted to withstand mechanical load and provide low friction moveable joints. Appreciate the differences/similarities between ligaments and tendons. Be aware of examples of disorders of connective tissues where the extracellular matrix (ECM) is implicated: osteoarthritis (OA), scurvy, osteogenesis imperfecta (‘Brittle bone disease’). Types of cartilage Hyaline Cartilage eg articular cartilage On surfaces of moveable joints - glassy/shiny appearance, low friction surface Withstands compressive and tensile forces - load-bearing but not elastic Pliable - spreads loads over ends of bones Collagen - mainly basketwave Cells of connective tissue 1 Cells of connective tissue 2 Cells of connective tissue 3  Fibrocartilage eg intervertebral discs, meniscus Support, prevents bone-bone contact, spread load, limits movement Can withstand tensile and compressive forces Collagen fibres thick & normally have clear parallel orientation and structure Cells often in rows, mainly fibroblasts but some chondrocytes Cells of connective tissue 4 Cells of connective tissue 5  Elastic cartilage eg auricle of ear, epiglottis Histologically very similar to hyaline but contains elastin also (which is highly and reversibly deformable Ideal for a flexible skeleton Fibroblasts synthesise elastin, collagens, small proteoglycans Roles of articular cartilage Absorbs / distributed load, protect ends of bone Cells of connective tissue 6  With synovial fluid, provides a low friction surface for articulating joints Synovial fluid Ultrafiltrate of plasma - with hyaluronic acid - lubricant Produced by synoviocytes of synovial membrane Primary source of nutrition & removal of waste for cartilage cells Viscous when joint immobile. ‘Warming-up’ exercises increases production/secretion, reduces viscosity. Smart lubrication Rheumatoid arthritis - autoimmune disease where immune system attacks synovium Phagocytes Close relationship between load and biological properties of connective tissues. Appear simple and homogenous - but complex and heterogenous Connective tissue is not inert but living and responsive to mechanical environment Load-bearing cartilage thicker & stronger than non-load-bearing In immobilised joint, cartilage thins and lost. Usually reversible Passive cycling does not maintain cartilage health Long-term static load does not maintain cartilage health Cells of connective tissue 7  Adaptations of tendons/ligaments to mechanical forces Tendons transmit load from muscle to bone Cells of connective tissue 8  Ligaments transmit load / give stability from bone to bone (they hold the skeleton together) Cells adapt to prevailing mechanical forces by modifying ECM synthesis Comparison between extracellular matrix composition of tendon passing over bone compared to tensile region Cells of connective tissue 9 Cells of connective tissue 10 Cells of connective tissue 11  Excessive load / impact can cause matrix damage and chondrocyte death. Cells of connective tissue 12 Cells of connective tissue 13  Matrix synthesis / breakdown is totally controlled by chondrocytes Normal dynamic loading: synthesis = breakdown Greater loading : synthesis > breakdown Less loading: Breakdown > synthesis Cartilage degeneration: Breakdown >> synthesis Impact/excessive loading can cause permanent cartilage damage Loading of connective tissue within physiological limits is essential for cartilage health Cells of connective tissue 14  Load on chondrocytes - what are the signals? Depends on type of load, static or dynamic Static load depresses synthesis Dynamic load stimulates synthesis Fluid flow / streaming potentials / ionic composition - static load High hydrostatic pressure - dynamic load Cells of connective tissue 15  Link between changes to the mechanical environment of cells and the cell’s response is termed mechanotransduction How is cartilage adapted to withstand load ? Articular cartilage has no vulnerable structures: avascular aneural alymphatic no epithelium at cartilage surface (otherwise would scape off) low cell density (1-10%) complex ECM highly resilient - adapted to compressive and tensile forces All these adaptations are essential for load-bearing by articular cartilage Cells of connective tissue 16  Principal components of articular cartilage Collagens Proteoglycans Interstitial fluid Chrondocytes Collagen More than 19 collagen types Hyaline contains mainly type II Fibrocartilage mainly type I Proteoglycans Aggrecan - monomers of GAG - highly sulphated and acidic - fixed negative charges Aggrecan attracts cations and water, repels anions and SWELL But, only swollen to ~20% of total Small proteoglycans tend not to be retained effectively by the hyaline cartilage matrix. Cells of connective tissue 17  Interstitial fluid Complex challenging and changing environment for chondrocyte controlled by PGs Chondrocytes Cells of connective tissue 18  Single resident cell type of hyaline cartilage Entirely responsible for ECM synthesis/breakdown Chondrocytes can synthesise the whole array of matrix proteins, growth factors and degradative enzymes There is no chondrocyte division in skeletally mature healthy cartilage Chondrocyte proliferation only occurs in late stage osteoarthritis Cells of connective tissue 19 Cells of connective tissue 20  Tendon (Force transmission) Ligament (Joint stabilisation) Short band of flexible fibrous connective tissue Flexible, inelastic cord of fibrous tissue connects two bones or cartilage or holds a joint which attached skeletal muscle to bone together Joins skeletal muscle to bone Joins a bone to another bone Found at ends of skeletal muscles Found in joints Inelastic and tough Elastic and strong Fibroblasts organised into continuous Fibroblasts are randomly scattered; weaving rows; long axis direction pattern Collagen fibres (98% type I) high Collagen fibres (90% type I; 10% type III) lower content - arranged in dense parallel content -densely arranged but in weaving bundles - long axis direction. pattern. Proteoglycans higher content. Proteoglyans low content Cells of connective tissue 21  Low elastin content High elastin content Excessive pressure/stretch may cause Excessive pressure/stretch may cause torn tendinitis, tenosynovitis and avulsion ligaments and sprains Scar tissue has reduced flexibility and so this means that it may work effectively Cells of connective tissue 22 Cells of connective tissue 23 Cells of connective tissue 24  Damage to collagen type IX could explain cartilage swelling in early OA Cells of connective tissue 25 Cells of connective tissue 26  Scurvy - disorder of connective tissue involving the ECM Vitamin C deficiency Poor wound healing, hair and tooth loss, capillary weakness, stunted growth May be fatal because of increased risk of infection / bleeding Vitamin C in diet is essential as humans and some animals do not produce vitamin C Vitamin C is a key co-factor for the hydroxylation of collagens Reduced hydroxylation of prolyl amino acids leads to reduced collagen cross- linking and tissue weakness Scurvy is common in 3rd world countries and with refugees Cells of connective tissue 27  Osteogenesis imperfecta (Brittle Bone Disease, BBD) Crumpled bones, deformities and weakness, early fractures perinatal death Genetic disorder - due to mutations in collagen gene (mainly Type I collagen) Treatment with bisphosphonates (also used for osteoporosis) Different underlying mechanism compared to osteoporosis (OP) In Summary The cells of connective tissues are very sensitive to physico-chemical signals (i.e. mechano-transduction) and respond by producing an appropriate load- bearing ECM. (‘Form Follows Function’). The composition and properties of the various cartilages (hyaline cartilage, fibrocartilage & elastic cartilage) are varied and depend on physiological function. The extracellular matrix (ECM – comprising collagens, proteoglycans, elastin and interstitial fluid) is complex and the proteins are turned over (by synthesis/degradation) by the resident connective tissue cells. High levels of mechanical load can be injurious to connective tissues potentially causing post-traumatic osteoarthritis (PTOA). Low levels of load can lead to mechanically-weakened connective tissues (disuse osteoporosis). Cells of connective tissue 28  Damage to collagens underlies development of OA, scurvy and osteogenesis imperfecta (brittle bone disease). Cells of connective tissue 29