Basic Science Flashcards
Bone Cells: Osteoblasts
- Origin
- Structure
- Function
- Bone non-mineralised matrix consists of: (4)
- mesenchymal stem cells ->differentiate into osteoprogenitor cells
- Contain increased amounts of endoplasmic reticulum, Golgi apparatus, and mitochondria than other cells ◦allows for synthesis and secretion of bone matrix
- Form bone by producing non-mineralized matrix and regulate osteoclast function
- ◾ALP ◾ Col Type 1 ◾osteonectin ◾osteocalcin ◾stimulated by 1,25 dihydroxyvitamin D
Bone Cells: Osteoblasts
Signaling : osteoblastic differentiation
- ___ stimulates mesenchymal cells to become osteoprogenitor cells
- . _________ plays a major role in formation of osteoblasts with resulting intramembranous bone formation
- GFs ___ and ___ induce osteoblast differentiation
- BMP
- stable beta-catenin
- Platelet derived growth factor (PDGF) AND insulin derived growth factor (IDGF) induce osteoblast differentiation
** note: core binding factor alpha-1 (cbf alpha -1: RUNX2) also plays a role in osteoblast differentiation
Bone Cells: Osteoblasts
Signaling : osteoblast bone production
- PTH receptor stimulates production of: (2)
- 1,25 dihydroxyvitamin D receptor stimulates (3)
- Stimulates alkaline phosphatase and type I collagen production
- Stimulates matrix and alkaline phosphatase synthesis
and production of bone specific proteins (osteocalcin)
Bone Cells: Osteoblasts
Signaling : osteoblast bone production
- Estrogen inhibits ______ and stimulates ________ by inhibiting ________
- Glucocorticoids inhibit ______and _____ production
- prostaglandins stimulate bone _______ by activating _______
- (a) bone resorption; (b) bone production; (adenylyl cyclase)
- (a) collagen; (b) bone matrix
- (a) bone resorption; (b) adenylyl cyclase
Bone Cells: osteoblasts role in–> osteoclast signaling
(note: interconnected signaling allows coupling of bone resorption and formation)
- osteoclast activation pathway
- osteoclast inhibition pathway
◾PTH receptors on osteoblast bind to PTH which when leads to expression of RANKL
◾RANKL binds to RANK receptor on osteoclast and bone resorption
- ◾osteoblasts can secrete OPG (osteoprotegrin)
◾OPG binds to RANKL on the osteoblast, preventing RANK activation ◾inhibits osteoclast activity
Bone Cells: osteoblasts role in–> regulation of hematopoietic cells and immune response
Occurs through the Jagged1-Notch pathway (explain)
◾PTH induces Jagged1 on osteoblasts
◾Jagged1 stimulates Notch receptors on the membrane of hematopoietic stem cells which results in cell proliferation
Bone Cells: osteoblasts
Location
- More metabolically active cells at the _________
- More metabolically active cells at the BONE SURFACE
Note: less active cells in more central bone -> activated by disruption of the more peripheral osteoblasts
Bone Cells: osteoclasts
Function is to reabsorb bone:
- regulated by _________
- Steps in resorption
- Osteoblasts regulate osteoclast bone reabsorbtion (see above)
- Steps in resorption :
i) migration to resorption site
ii) bone attachment
iii) polarization (formation of membrane domains)
iv) dissolution of hydroxyapatite
v) degradation of organic matrix
vi) removal of degradation products from resorption lacuna
vii) apoptosis of the osteoclasts or return to the non-resorbing stage.
Bone Cells: osteoclasts
- Origin
- Cellular anatomy / histology
- Originate from myeloid hematopoietic cells from monocyte/macrophage cell lineage (Monocyte progenitors fuse together to form mature multinuclear cells)
- Multinucleated giant cells
Bone Cells: Osteoclasts
Cellular physiology
- Bone reabsorbtion occurs at _______.
- What are Howship’s lacunae?
- Tartrate resistant acid phosphate:
a) secreted by ______ ?
b) Effect on pH ?
c) Effect on solubility of hydroxyapatite crystals - Proteolytic digestion removes the organic matrix. One of the major proteolytic enzyme that degests organic matrix at ruffled border is _________
- Bisphosphonates mechanism? ◾prevents osteoclasts from forming ruffled border and producing acid hydrolases
- Ruffled border
- Site of bone resorption where ruffled border meets bone surface
3a. Secreted by osteoclasts to lower the Ph (utilizing carbonic anhydrase [CA])
3b. increases the solubility of hydroxyapatite crystals (def of CA prevents bone resorption)
- Cathepsin K
- Prevents osteoclasts from forming ruffled border and producing acid hydrolases
Bone Cells: Osteoclast-osteoblast signaling
Osteoblasts upregulate and downregulate osteoclast activity
Role of:
- RANK-L
- IL-1
- Calcitonin
- IL-10
- Osteoclast activation
◾RANKL (NF-kB ligand) ◾expressed by osteoblasts and tumor cells to activate osteoclasts - IL-1 ◾found adjacent to loose total joint implants and known to activate osteoclasts
- Osteoclast inhibition
- Osteoclast inhibition
Bone Cells: Osteocytes
- Origin
- Account for _% of cells in mature skeleton
- Structure
a) ____ nucleus to cytoplasm ratio
b) have long cellular processes which communicate with other cells via _______in the bone
- Former osteoblasts trapped in the matrix they produced
- 90%
3a. High
3b. Canalculi
Bone Cells: Osteocytes
Function
- Maintain ________?
- Important in regulation of ____ and ______ concentrations in bone
- Do not express __________
Signaling
- Stimulated by _______
- Inhibited by _____
- Communicate with adjacent osteocytes via ___ junctions in _______
- Maintain bone and cellular matrix
- Calcium and phosphorous
- Alkaline phosphatase
- Calcitonin
- PTH
- Gap; Canaliculi
Bone Cells: Osteoprogenitor Cells
- Origin
- Function
a) become ________ under low strain and high oxygen tension
b) become ________ under intermediate strain and low oxygen tension
c) become _______ tissue under high strain
- Origin
◦originate from MSC’s
◦environment will determine their function - Function
a) Osteoblasts
b) Cartilage
c) Fibrous
Bone Matrix
Bone is made up of (2)
Bone is made up of
- organic component ◾40% of dry weight
- inorganic component ◾60% of dry weight
Bone Matrix: Organic component
Components include (4)
1. Collagen ◾90% of organic component ◾primarily type I collagen ◾provides tensile strength ◾it is a triple helix composed of one alpha-2 and two alpha-1 chains
- Proteoglycans
◾responsible for compressive strength
◾inhibit mineralization
◾composed of glycosaminoglycan-protein complexes - Matrix proteins
◾includes noncollagenous proteins
◾function to promote mineralization and bone formation - Cytokines and growth factors
Bone Matrix: matrix proteins
Includes noncollagenous proteins that function to promote mineralization and bone formation
Three main types of proteins involved in bone matrix ?
- Osteocalcin : most abundant non-collagenous protein in the matrix (10%-20% of total) produced by mature osteoblasts
◾promotes mineralization and formation of bone
◾directly involved in regulation of bone density
◾attracts osteoclasts
◾clinical application = marker of bone turnover; can be measured in urine or serum - Osteonectin:
◾secreted by platelets and osteoblasts
◾function = believed to have a role in regulating calcium or organizing mineral in matrix - Osteopontin ◾function ◾cell-binding protein
Bone Matrix: cytokine and growth factors
- Role ?
- Include which GF/Cytokine
- Role of cytokine and growth factors
◾small amounts present in matrix
◾aid in bone cell differentiation, activation, growth, and turnover - Include
◾IL-1, IL-6, IGF, TGF-beta, BMPs
Bone Matrix : Inorganic component
- Components (2)
Components include
- Calcium hydroxyapatite (Ca10(PO4)6(OH)
◾provides compressive strength - Osteocalcium phosphate (brushite)
Bone Matrix: Bone Circulation
- Bone receives __to__% of cardiac output
- Bones with tenuous blood supply (4)
- Name the three sources of blood supply to long bones
- 5-10%
- ◦scaphoid ◦talus ◦femoral head ◦odontoid
- Blood supply to long bones:
i) nutrient artery system
ii) metaphyseal-epiphyseal system
iii. ) periosteal system