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Updated: 8/17/2021

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 αVβ3 and 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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(OBQ14.87) The Arg-Gly-Asp (RGD) sequence of extracellular bone proteins directly allows which of the following?

QID: 5497

Interaction with integrins

60%

(1924/3220)

Chemoattraction of osteoclasts

19%

(598/3220)

Binding to vinculin protein

8%

(246/3220)

Attachment site of Sharpey's fibers

9%

(296/3220)

Decrease in bone stiffness

3%

(110/3220)

L 3 C

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

QID: 4599
FIGURES:

Originates from hematopoietic cells from a macrophage lineage

79%

(3243/4125)

Derived from undifferentiated mesenchymal cells

11%

(435/4125)

They are former osteoblasts trapped in the matrix they produced

4%

(172/4125)

They become cartilage under intermediate strain and low oxygen tension

2%

(78/4125)

They form bone by producing non-mineralized matrix

4%

(167/4125)

L 1 A

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(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?

QID: 2817

neutrophils

2%

(67/3031)

lympocytes

1%

(23/3031)

plasma cells

2%

(74/3031)

osteoblasts

3%

(80/3031)

osteoclasts

92%

(2781/3031)

L 1 C

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

QID: 757

Reduction of disulfide bonds in the extracellular matrix

26%

(787/3010)

Bone resorption

54%

(1635/3010)

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

12%

(352/3010)

Antagonize the action of RANK

7%

(196/3010)

Absorb water in the extracellular matrix

1%

(28/3010)

L 1 D

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

QID: 709

Osteoclasts

8%

(93/1134)

Monocytes

4%

(51/1134)

Myofibroblasts

1%

(16/1134)

Osteoblasts

84%

(957/1134)

Lymphocytes

1%

(15/1134)

L 1 D

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

QID: 769

Osteocalcin

76%

(1369/1795)

TGF-B

6%

(109/1795)

COLIIA1

8%

(138/1795)

cFOS

6%

(103/1795)

IL-1

4%

(68/1795)

L 1 D

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

QID: 368

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

23%

(179/786)

Chemotaxis of mesenchymal stem cells to sites of skeletal fractures

13%

(105/786)

Tumor-induced osteolysis

7%

(54/786)

Osteoclastic apoptosis

6%

(51/786)

Osteoblastic differentiation

50%

(392/786)

L 4 D

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

QID: 1120

Volkmann canals

14%

(508/3522)

Cement lines

1%

(26/3522)

Secondary messenger systems

2%

(53/3522)

Canaliculi

51%

(1785/3522)

Haversian canals

32%

(1127/3522)

L 1 C

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

QID: 1136

Osteoclasts

63%

(715/1142)

Chondrocytes

7%

(82/1142)

Adipocytes

21%

(235/1142)

Osteoblasts

4%

(43/1142)

Fibroblasts

5%

(53/1142)

L 1 C

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

QID: 1084

Interacts with RANK Ligand to stimulate osteoclasts

8%

(82/1041)

Osteoclasts attaching to bone

50%

(519/1041)

Competitive inhibition of RANK Ligand

6%

(60/1041)

Chemotaxis in fracture healing

25%

(265/1041)

Type II collagen formation

10%

(109/1041)

L 1 D

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EXPERT COMMENTS (37)
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