Updated: 4/21/2019

Bone Cells

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https://upload.orthobullets.com/topic/9002/images/Osteoblast_moved.jpg
https://upload.orthobullets.com/topic/9002/images/osteoclast.jpg
https://upload.orthobullets.com/topic/9002/images/osteocyte.jpg
https://upload.orthobullets.com/topic/9002/images/osteoprogenitor cells.jpg
Osteoblasts
  • Origin
    • derived from undifferentiated mesenchymal cells 
    • mesenchymal cells then differentiate into osteoprogenitor cells
  • Structure
    • contain increased amounts of endoplasmic reticulum, Golgi apparatus, and mitochondria than other cells
    • allows for synthesis and secretion of bone matrix
  • Function
    • form bone by producing non-mineralized matrix
      • alkaline phosphatase
      • type I collagen
      • osteonectin
      • osteocalcin  
        • stimulated by 1,25 dihydroxyvitamin D
    • regulate osteoclast function 
  • Signaling
    • osteoblastic differentiation
      • BMP stimulates mesenchymal cells to become osteoprogenitor cells
      • core binding factor alpha-1 (cbf alpha -1: RUNX2)  
      • stable beta-catenin plays a major role in inducing cells to form osteoblasts with resulting intramembranous bone formation 
      • platelet derived growth factor (PDGF) induces osteoblast differentiation
      • insulin derived growth factor (IDGF) induces osteoblast differentiation
    • osteoblast bone production
      • PTH receptor
        • stimulates alkaline phosphatase and type I collagen production
      • 1,25 dihydroxyvitamin D receptor 
        • stimulates matrix and alkaline phosphatase synthesis
        • production of bone specific proteins (osteocalcin)
      • estrogen inhibits bone resorption and stimulates bone production by inhibiting adenylyl cyclase
      • glucocorticoids inhibit collagen and bone matrix production 
      • prostaglandins stimulate bone resorption by activating adenylyl cyclase
    • osteoclast signaling 
      • interconnected signaling allows coupling of bone resorption and formation 
      • osteoclast activation
        • PTH receptors on osteoblast bind to PTH which when leads to expression of RANKL 
        • RANKL binds to RANK receptor on osteoclast and bone resorption
      • osteoclast inhibition
        • osteoblasts can secrete OPG (osteoprotegrin)
        • OPG binds to RANKL on the osteoblast, preventing RANK activation
          • inhibits osteoclast activity 
    • regulation of hematopoietic cells and immune response
      • occurs through the Jagged1-Notch pathway
        • PTH induces Jagged1 on osteoblasts 
        • Jagged1 stimulates Notch receptors on the membrane of hematopoietic stem cells which results in cell proliferation
  • Location
    • more metabolically active cells at the bone surface
    • less active cells in more central bone
      • activated by disruption of the more peripheral osteoblasts
Osteoclasts 
  • Function
    • reabsorb bone
      • osteoblasts regulate osteoclast bone reabsorbtion (see above)
      • steps in resorption cycle 
        • migration to resorption site
        • bone attachment
        • polarization (formation of membrane domains)
        • dissolution of hydroxyapatite
        • degradation of organic matrix
        • removal of degradation products from resorption lacuna
        • apoptosis of the osteoclasts or return to the non-resorbing stage.  
  •  Origin
    • originate from myeloid hematopoietic cells from monocyte/macrophage cell lineage  
    • monocyte progenitors fuse together to form mature multinuclear cells
  • Cellular biology
    • cellular anatomy
      • multinucleated giant cells  
    • cellular physiology
      • bone reabsorbtion occurs at ruffled border
        • Howship's lacunae
          • are site of bone resorption where ruffled border meets bone surface
        • tartrate resistant acid phosphate
          • secreted by osteoclasts to lowers the Ph (utilizing carbonic anhydrase) and increases the solubility of hydroxyapatite crystals
            • deficiency of carbonic anhydrase prevents bone resorption 
        • proteolytic digestion
          • the organic matrix is then removed by proteolytic digestion
          • cathepsin K
            • is one major proteolytic enzyme that degests organic matrix at ruffled border 
        • bisphosphonates mechanism
          • prevents osteoclasts from forming ruffled border and producing acid hydrolases
  • Molecular biology
    • osteoclast-bone attachment
      • osteoclast attaches to bone matrix at sealing zone
      • attach to bone surfaces via integrins on osteoclast surface   
        • integrins include αVβ3, αVβ5, α2β1, αVβ1 
          • αVβ3 (on osteoclast) is a receptor for vitronectin (on bone surface)    
          • Arg-Gly-Asp (RGD) sequence of extracellular bone proteins directly allows binding to integrins   
            • antibodies to αVβand RGD inhibit bone resorption 
    • osteoclast polarization  
      • contain specialized membrane domains
        • ruffled border (RB)
        • functional secretory domain (FSD)
        • basolateral membrane (BL)
    • mineralized bone matrix degradation
      • hydroxyapatite crystals dissolved by HCl secreted through ruffled border into resorption lacuna (RL)
        • RL is an extracelllular space between RB and bone matrix, sealed from ECF by sealing zone
        • uses ATP-consuming proton pumps in RB and in intracellular vacuoles
          • H+ come from carbonic anhydrase II
        • RB has high number of chloride channels (maintain electroneutrality)
    • organic bone matrix degradation
      • lysosomal cysteine proteinases 
      • matrix metaloproteinases (MMPs), esp MMP-9
      • cathepsin K
        • mutation in cathepsin K gene leads to pycnodysostosis
    • removal of degradation products
      • by transcystosis to FSD, where they are secreted into ECF
      • tartrate-resistant acid phosphatase (TRAP) is localized in transcytotic vesicles, generates reactive O2 species that destroys collagen
    • osteoclast-osteoblast signaling
      • osteoblasts upregulate and downregulate osteoclast activity
        • 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
          • calcitonin
          • IL-10
Osteocytes  
  • Origin
    • are former osteoblasts trapped in the matrix they produced
    • account for 90% of cells in the mature skeleton
  • Structure
    • high nucleus to cytoplasm ratio
    • have long cellular processes which communicate with other cells via canalculi in the bone
  • Function
    • maintain bone and cellular matrix
    • important in regulation of calcium and phosphorous concentrations in bone
    • do not express alkaline phosphatase
  • Signaling
    • stimulated by calcitonin
    • inhibited by PTH
    • communicate with adjacent osteocytes via gap junctions in canaliculi 
Osteoprogenitor Cells
  • Origin
    • originate from mesenchymal stem cells
    • environment will determine their function
  • Function
    • become osteoblasts under low strain and high oxygen tension
    • become cartilage under intermediate strain and low oxygen tension
    • become fibrous tissue under high strain
 

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(OBQ12.239) Which of the following is true regarding the cell seen in Figure A? Review Topic

QID: 4599
FIGURES:
1

Originates from hematopoietic cells from a macrophage lineage

78%

(2543/3258)

2

Derived from undifferentiated mesenchymal cells

11%

(357/3258)

3

They are former osteoblasts trapped in the matrix they produced

4%

(130/3258)

4

They become cartilage under intermediate strain and low oxygen tension

2%

(68/3258)

5

They form bone by producing non-mineralized matrix

4%

(136/3258)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(OBQ05.234) Which system of lacunar networks is used among osteocytes to communicate? Review Topic

QID: 1120
1

Volkmann canals

15%

(424/2846)

2

Cement lines

1%

(20/2846)

3

Secondary messenger systems

1%

(41/2846)

4

Canaliculi

49%

(1407/2846)

5

Haversian canals

33%

(938/2846)

ML 4

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PREFERRED RESPONSE 4

(OBQ06.182) What is the function of the core binding factor alpha-1 (Cbfa1/Runx2)? Review Topic

QID: 368
1

Phosphorylation and intracellular activation of signal transducers and activators of transcription (STATs)

22%

(91/414)

2

Chemotaxis of mesenchymal stem cells to sites of skeletal fractures

13%

(52/414)

3

Tumor-induced osteolysis

7%

(27/414)

4

Osteoclastic apoptosis

7%

(28/414)

5

Osteoblastic differentiation

51%

(213/414)

ML 4

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ07.96) Cathepsin K is an enzyme produced by osteoclasts. What is the function of cathepsin K? Review Topic

QID: 757
1

Reduction of disulfide bonds in the extracellular matrix

26%

(594/2309)

2

Bone resorption

55%

(1259/2309)

3

Activation of RANK (Receptor activator of nuclear factor kappa-B)

12%

(269/2309)

4

Antagonize the action of RANK

7%

(161/2309)

5

Absorb water in the extracellular matrix

1%

(19/2309)

ML 4

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PREFERRED RESPONSE 2

(OBQ07.48) Which of the following cell types releases osteoclastogenic cytokines such as RANKL? Review Topic

QID: 709
1

Osteoclasts

10%

(62/648)

2

Monocytes

5%

(31/648)

3

Myofibroblasts

2%

(11/648)

4

Osteoblasts

82%

(533/648)

5

Lymphocytes

1%

(9/648)

ML 1

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PREFERRED RESPONSE 4

(OBQ05.250) Mesenchymal stem cells have the capacity to differentiate into all the following cell types EXCEPT? Review Topic

QID: 1136
1

Osteoclasts

59%

(398/669)

2

Chondrocytes

7%

(48/669)

3

Adipocytes

23%

(155/669)

4

Osteoblasts

4%

(28/669)

5

Fibroblasts

4%

(28/669)

ML 3

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PREFERRED RESPONSE 1

(OBQ07.108) Which gene or protein is the most specific marker of mature osteoblasts but is not expressed by immature, proliferating osteoblasts? Review Topic

QID: 769
1

Osteocalcin

81%

(910/1126)

2

TGF-B

4%

(41/1126)

3

COLIIA1

7%

(74/1126)

4

cFOS

5%

(54/1126)

5

IL-1

4%

(42/1126)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(OBQ05.198) Vitronectin is an important receptor involved in which of the following functions? Review Topic

QID: 1084
1

Interacts with RANK Ligand to stimulate osteoclasts

8%

(34/425)

2

Osteoclasts attaching to bone

51%

(215/425)

3

Competitive inhibition of RANK Ligand

4%

(17/425)

4

Chemotaxis in fracture healing

28%

(118/425)

5

Type II collagen formation

9%

(40/425)

ML 3

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PREFERRED RESPONSE 2

(OBQ09.4) Microscopic description of "multinucleated giant cells that originate from monocyte lineage and possess a ruffled border" best describe which of the following cell types? Review Topic

QID: 2817
1

neutrophils

2%

(39/2416)

2

lympocytes

0%

(10/2416)

3

plasma cells

2%

(53/2416)

4

osteoblasts

2%

(49/2416)

5

osteoclasts

94%

(2259/2416)

ML 1

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PREFERRED RESPONSE 5
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