B4 Bone and cartilage Flashcards
role of bone tissue
-support and locomotion
-protection of vital organs
-contain bone marrow for hematopoiesis
-reservoir for minerals (Ca, Pi, Mg)
tissue-specific characteristics of bone (3)
- very dynamic (remodelling via mineralisation and reabsorption)
- Very dense (for strength and resistance)
- Highly vascularised (10% of blood from heart)
cells in bone tissue (4)
- stem cells (osteoprogenitors that form osteoblasts)
- osteoblasts (secrete ECM during mineralisation for bone formation)
- osteocytes (final irreversible form of osteoblasts)
- osteoclasts (bone reabsorption via osteolysis)
what is the organic portion of bone ECM made of
65% OF WEIGHT: CALLED THE OSTEOID:
-collagen type 1 (90%)
-proteoglycans / GAGs (decorin and biglycan)
-Multiadhesive GPs: osteonectin and osteopontin
-Bone specific proteins: osteocalcins and matrix GLA protein
-GFs and cytokines: IGFs, TNF, TGF, PDGF, inteleukins, RANKL
what is the inorganic portion of bone ECM made of
35% OF WEIGHT:
-crystals of hydroxyapatite (calcium and phosphate): arranged along collagen type 1 fibrs an keep bone stiff
what is the origin of the bone cells
Osteoblasts = from MSC (mesenchymal stem cells)
Osteoclasts = from HSC (Hematopoietic stem cells)
!! diff TFs induce different pathways of differentiation
what controls homeostatis of bone remodelling
DEPENDENT ON: ratio between mineralisation and reabsorption
HORMONAL AGENTS:
-parathyroid increases bone resorption (activated osteoclasts), calcitonin blocks activity of osteoclasts
-growth hormones and gonadal steroids activate osteoblasts and increase bone formation, glucocorticoids block osteoblasts
describe the structure of an osteoclast
- RUFFLED BORDER: direct concact with bone, membrane infoldings containing H+ pumps (increases area for exocytosis of enzymes and H+ secretion).
- SEALING ZONE: area on each side of the ruffled border that attaches osteoclast to the bone surface to provide a tight seal: integrin of osteoclast binds to vitronectin on bone surface
- BASOLATERAL REGION: contains receptors (RANKL, channels and Gproteins)
!! osteoclasts are multinucleated
describe the process of osteolysis
- osteoblast production of RANKL which binds to the receptor on osteoclast
- low pH (4) achieved using H+-ATPases for the mobilisation of Ca and Pi
- removal of OH groups from hydroxyapatite in ECM which destroys (solubilises) crystals
- causes demineralisation
How are alkaline conditions prevented during osteolysis
-carbonic anhydrase enzymes inside osteoclast release H+ and HCO3-
-VATPASE (membrane enzyme) secretes H+ to bone surface
-concentration of bicarbonate is controlled by a basolateral Cl/HCO3- exhanger so that alkalosis is prevented
describe the process of mineralisation
- formation of matrix vesicles released by osteoblasts (containing Ca, K, Pi, enzymes, pyrophosphate for energy and alkaline phosphatase)
- Ca2+ associates with collagen fibers in the ECM for mineralisation
what are the biochemical markers that signify bone turnover
FACTORS RELEASED BY OSTEOCLASTS AND OSTEOBLASTS:
-osteocalcin
-osteonectin
-alkaline phosphatases
-collagen propeptides (bcos they signify collagen breakdown)
role of osteocalcin
FUNCTION: regulation of hydroxyapatite size and shape, produced by osteoblasts
PRODUCED IN 2 FORMS:
1. carboxylated glutamic acid form: binds to Ca2+ and hydroxyA crystals, is vitamin K dependent, and determines bone quality (acts as resin to hold bone together)
- uncarboxylated osteocalcin: low affinity for hydroxyA and is released into circulation to act as hormone (not vitaminK dependent)
properties of cartilage (3)
-avascular, hence low metabolic rate and poor healing abilities
-high tensile strenth due to collagen fibers
-resistance to compression bcos of proteoglycans which can bind to water
what is the role of alkaline phosphatases
TNAP - tissue non specific AP (zinc containing) calcifies bones: hydrolyses pyrophosphate and supplies Pi to enhance mineralisation
!! present in the matrix vesicles secreted by osteoblasts
