1.7 Tissue and bone adaptation Flashcards
What makes a connective tissue?
Extracellular matrix (ECM) = network of discreetly secreted macromolecules which maintain cell/tissue integrity Rich in fibrous proteins Glycoaminoglycans (GAG) - polysaccharides which usually link with proteins - proteoglycans
What are properties of hyaluronan/hyaluronic acid?
GAG,
- very large molecule
- high affinity for water (hydrophilic)
- tissue viscosity
- excellent lubricative properties
- important in tissue repair/linked to tumour progression
What are properties of Chondroitin sulphate/keratan sulphate?
Highly charged sulphate groups provide electrostatic repulsion and high anti compressive properties
What is elastin?
Protein with a coiled structure
- cross links between molecules
- give elastin its characteristic elastic properties
What is Collagen?
Major component of ECM
Triple helix of polypeptide chains to form collagen microfibril
microfibril - fibrils - fibres
- high tensile strength
- complaint - arrangement of fibrils and CRIMP
- 29 forms
Describe the structure of a tendon
Collagen - predominantly type I - 86% Proteoglycans 1-5% Elastin 2% Cells: tenocytes (specialised fibrocytes) Water
Describe the structure of a ligament
Fibrocytes plus ECM
Similar to tendon but lower (~75%) collagen component, more proteoglycan
Slight differences in collagen types/organisation
Describe the composition of cartilage
Cells = chondrocytes
Collagen ~ 10-20%, type II mostly (90%), but also III, IV XII and XIV
Predominant proteoglycan (10-20%) is chondroitin sulphate
Hylauronan
68% water
Regional variation
Describe the structure of a chondrocyte
Spheroid in shape - except surface
Synthesise type II collagen, large proteoglycan aggregates and non - collagenous proteins
Depend on anaerobic metabolism
Mechanical joint loading influences the functions of chondrocytes
How is cartilage adapted in the superficial (tangential) zone?
85% collagen, orientated tangential to surface
Greatest ability to resist shear stresses
How is cartilage adapted in the middle (transitional) zone?
Transition between shearing forces of surface to compression forces in deep layer; collagen arranged obliquely
Composed largely of proteoglycans
How is cartilage adapted in the deep (radial) zone?
Collagen fibres attached radially (vertical) into the tidemark - distributes loads and resists compression: high PG content
What are osteocytes?
support and maintain bone structure
What are osteoblasts?
synthesise bone matrix
What are osteoclasts?
absorb bone
What is Wolff’s Law?
Stresses caused by ligaments and muscles = stresses on the tissue
- signals to osteocytes to stimulate/send signals to osteoblasts to produce greater bone tissue to resist that load + reduce stresses
How are trabeculae orientated?
Not randomly orientated but are orientated along the axis of high stress and strain
- parallel to major axis of stress and strain to resist and even out the loading on the bone
What if you continually stress a tissue?
Fracture, rupture or failure ‘ultimate’ stress and strain
Describe the relationship of ECM and cells
- Matrix can influence cell shape, survival and proliferation
- Matrix influences cell behaviour by binding to cell surface receptors that activate intracellular signalling pathways
- Continuous turnover of ECM - matrix macromolecules degraded and resynthesised
What is intramembranous ossification?
- Mesenchymal cells (stem cells by de noro method) become osteoblasts which then secrete osteoid (bone precursor tissue, but due to no ECM surrounding it, it produces pre-mineralised matrix)
- Osteoblasts trapped in mineralised matrix become osteocytes
How do long bones form?
Long bones form from cartilage template
Describe the process of long bone formation - intramembranous ossification
Perichondrium lays down bone on cartilage in diaphysis region (mesenchymal cells differentiate into bone precursor cells and lay down bony tissue, gets mineralised forms a collar around the long bone)
Describe the process of long bone formation - endochondral ossification
Cartilage at centre of shaft degenerates; vascularisation; matrix becomes impregnated with calcium salts
How do bones grow in length?
Elongating in the diaphysis region
- cells increase in no. + size
- hypertrophied cells = enlarged and either excrete a large amount of matrix or change fates
Stages in bone growth at the growth plate
- Proliferation and maturation of cartilage cells
- Hypertrophy of chondrocytes
- Calcification of cartilage matrix
- Depolarisation of bone on cartilage template
- Organisation of bony trabeculae and their osteoclastic resorption
How does the bone grow in girth?
More lamellae/osteons created as the bone widens
What are nutritional influences on bone?
Dietary calcium and phosphate salts
Absorption depends on calcitriol - only made in the presence of vitamin D
Vitamins C,A,K and B12
What are hormonal influences on bone?
Calcitonin and parathyroid hormone - calcium metabolism regulation
Insulin growth hormone, thyroxine - bone growth
Oestrogen - growth plate closure (testosterone); osteoblast activity
What is bone modelling?
the process of bone shape change in response to the loads imposed
What is bone modelling?
A lifelong cyclical process of bone removal and addition
What is the cyclical process?
Osteoclasts form and attach bone to matrix
- resorption = osteoclasts secrete enzymes which break down bone. Osteoclast apoptosis
- reversal = Area is populated by osteoblasts
- formation = osteoblasts synthesise organic matrix. Osteoblasts regulate mineralisation of matrix. Osteoblasts entombed in matrix become osteocytes
