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MSK (Bone Biology (Bone formation: (ALP: Alkaline phosphatase
Enzyme…
MSK
Bone Biology
Organic component
- Osteoid 1) 90% type 1 collagen
2) 10% GAGs
Inorganic component
- Hydroxyapatite = Ca(PO)(OH)
- Osteoprogenitor: 'Founding fathers', precursor for osteoblasts
- Osteoblast:Bone makers. Very few in number. Precursor for osteocytes: bone producers
- Osteocyte: resident Bone cells: most numerous (95%), strike balance between bone formation and resorption: type 1 collagen make up ECM, in bone
- Osteoclast: Bone resorbers. From pro-monocyte cell lines: multinucleated
Bone formation:
ALP: Alkaline phosphatase
- Enzyme released osteoblasts
- Found everywhere, more concentrated in liver, bile ducts, kidney and bone
- bone: splits pyrophosphate into 2 phosphates
- More phosphate binds with calcium, more calcium phosphate and more hydroxyapatite
- More hydroxyapatite: more bone precipitation
- By releasing ALP: osteoblasts help bone formation
Osteoclast activation
- PTH stimulates bone resorption by osteoclasts
- Receptors for PTH on osteoblasts
- Signal to osteoclast precursors fusion, diff and activation
- Osteoclast precursors express RANK
- Osteoblast express RANKL
- Osteoblasts also release osteoprotegerin: protects bone : deocy receptor for RANKL
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Sclerostin
- Protein secreted by osteocytes
- Inhibits bone formation by blocking RANK receptor
Bone remodelling
- Osteocytes: mechanosensory- Sense load on bone
- Osteocytes signal for osteoclast maturation and diff
- Osteoprogenitors for osteoblast: can produce osteoid
- Calcification of bone matrix with hydroxyapatite occurs over 6 motns
Calcium regulation
2.2-2.5 mmol/L
Hypercalcaemia: cardiac arrest and coma: nerves less excitable
Hypocalcaemia: decrease in CO and tetany: nerves more excitable
- Decrease in Ca
- Causes Parathyroid gland to release PTH
Increase Ca , negative feedback PTH
Kidney
- Ca resorption (ascending loop henle)
- PO4 excretion
(PCT)
- 1-hydroxylase (PCT)
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7-Dehydroxycholesterol (cholosterol precurso): converted to vitamin D3 (cholecalciferol/calcitriol) in skin from UV light
- Vit D3 Converted to 1,25-(OH)2-D3 by 1-hydroxylase (kidney) and 25-hydroxylase (liver)
(neg feedback PTH)
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Decrease blood calcium
- Blood Ca too high, calcitonin release
- From parafollicular cells
- Inhibits osteoclasts: no bone resorption
- Inhibits calcium absorption in SI
- Inhibits calcium absorption kidneys
Collagen formation
- Pro-collagen formed in the cell. Trial helix structure, with 1 alpha and 2 beta chains (assembly in Er)
- Upon formation cell, pro-collagen secreted in ECM
- In ECM, pro collagen cleaved at N and C terminal (non helical segments), final collagen molecule
- Collagen molecules cross link form fibrils, which cross link to form fibres
28 Types
90% type 1
- Type 1 collagen: Skin, tendons, around vasculature, bone and organs (antecubital fossa)
- Type 2 collagen: cartilage
Types of cartilage
Elastic
- Made of: Type 2 collagen
- Type of protein: Elastin
- Found: Nose and ear
Fibrous
- Made from: Only one which contains both type 1 and type 2 collagen + fibrous tissue
- Found: Intervertebral discs, pubic symphysis
- Lacks: true perichondrium
Hyaline
- Found: Synovial joints
- Made of: Type 2 collagen + aggrecan
- Hurt: No, aneural
- Recovery: No, avascular
- Not calcified bone
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