• Bone Cells include Osteoblasts, Osteoclasts, Osteocytes and bone lining cells.

1. Osteoblasts

  • Osteoblast is the bone cells that are responsible for bone forming.
  • They appear as cuboid cells aligned in layers along immature osteoid.
  • Osteoblast activity stimulated by intermittent exposure to parathyroid hormone (PTH).
  • While its activity inhibited by tumor necrosis factor (TNF)-α.

Origin and Differentiation:

  • Osteoblasts are derived from undifferentiated mesenchymal stem cells.
  • Differentiation is stimulated by:
    1. Bone morphogenetic protein (BMP):
      • Stimulates Mesenchymal cells to become osteoprogenitor cells.
    2. Core-binding factor α-1 stimulates differentiation.
    3. β-Catenin stimulates differentiation into osteoblasts, with resulting intramembranous bone formation.
    4. Platelet-derived growth factor (PDGF).
    5. Insulin-like growth factor (IGF).

Functions:

  1. Form Bone.
  2. Regulating osteoclasts activity.

Location:

  • More metabolically active osteoblasts bone cells are located at the bone surface.
  • Less active bone cells are located in more central bone.

Osteoblasts produce the following:

  1. Alkaline phosphatase.
  2. Osteocalcin (stimulated by 1,25 dihydroxyvitamin D).
  3. Type I collagen.
  4. Bone sialoprotein.
  5. Receptor activator of nuclear factor (NF)-κB ligand (RANKL).
  6. Osteoprotegrin: binds RANKL to limit its activity.

Receptor Types on Osteoblasts:

Receptor TypeEffects
Parathyroid hormone PTH– Releases a secondary messenger (exact mechanism unknown) to stimulate osteoclastic activity
– Activates adenylyl cyclase
1,25(OH)2 vitamin D3 – Stimulates matrix and alkaline phosphatase synthesis and production of bone-specific proteins (e.g., osteocalcin)
Glucocorticoids– Inhibits DNA synthesis, collagen production, and osteoblast protein synthesis
Prostaglandins – Activates adenylyl cyclase and stimulates bone resorption
Estrogen– Has anabolic (bone production) and anticatabolic (prevents bone resorption) properties
– Increases mRNA levels for alkaline phosphatase
– Inhibits activation of adenylyl cyclase
Different Receptor Types on Osteoblasts and there effects

2. Osteoclast:

  • Osteoclast is the bone cells that are responsible for bone resorption.
  • They are a multinucleated irregular giant cells.

Origin and Differentiation:

  • Osteoclasts are derived from hematopoietic cells in macrophage lineage.
  • Monocyte progenitors fuse together to form mature multinuclear giant cells.

Function:

  • Bone resorption:
    • Bone resorption occurs in Howship lacunae.
    • Osteoclasts have a ruffled (brush-like) border and surrounding clear zone.
    • Border consists of plasma membrane enfoldings that increase surface area for resorption.
    • Cathepsin K
      • It is one major proteolytic enzyme that digests organic matrix at ruffled border.
  • Synthesize tartrate-resistant acid phosphate:
    • Secreted by osteoclasts to lowers the Ph and increases the solubility of hydroxyapatite crystals
  • Bind to bone surfaces through cell attachment proteins (integrins):
    • Integrins include αVβ3, αVβ5, α2β1, αVβ1.

Osteoclasts Activation:

  • Osteoclasts are activated by:
    1. IL-1:
    2. RANKL:
      • Osteoblasts express RANKL, which acts as follows:
        • Binds to receptors on osteoclasts.
        • Stimulates differentiation into mature osteoclasts.
        • Increases bone resorption.
  • Osteoclasts are Inhibited by:
    1. IL-10
    2. Calcitonin

IL1 is found in membranes surrounding loose total joint implants.

Bisphosphonates

  • Inhibit osteoclastic bone resorption by preventing osteoclasts from forming ruffled border and producing acid hydrolases.
  • Bisphosphonates is categorized into two classes on the basis of presence or absence of a nitrogen side group:
    1. Nitrogen-containing bisphosphonates:
      • It has up to 1000-fold more potent in their antiresorptive activity.
      • Zoledronic acid and alendronate.
      • Inhibit protein prenylation within the mevalonate pathway, blocking farnesyl pyrophosphate synthase.
      • Results in a loss of guanosin triphosphatase (GTPase) formation, which is needed for ruffled border formation and cell survival.
    2. Non–nitrogen-containing bisphosphonates:
      • Metabolized into a nonfunctional adenosine triphosphate (ATP) analogue, inducing apoptosis.
      • Decreases skeletal events in multiple myeloma.
      • Associated with osteonecrosis of the jaw.

Orthopedic uses of Bisphosphonate

  • Spine:
    • Reduced rate of spinal fusion in animal model.
    • Withholding bisphosphonate is recommended after surgery.
  • Hip and knee:
    • Safe for use in cementless hip arthroplasty and cemented knee arthroplasty;
    • May decrease rate of acetabular component subsidence.
  • Fracture healing:
    • No good data to recommend for or against use.

3. Osteocytes:

  • Osteocytes are bone cells that were former osteoblasts surrounded by newly formed matrix.
  • Osteocytes make up 90% of the bone cells in the mature skeleton.
  • Osteocytes cell has high nucleus/cytoplasm ratio.
  • It has a long interconnecting cytoplasmic processes projecting through the canaliculi:
    • Long Processes are used to communicate osteocytes with other bone cells.
  • Osteocytes stimulated by calcitonin.
  • While inhibited by PTH.

Functions:

  • Osteocytes maintain bone and cellular matrix.
  • Regulation of calcium and phosphorous concentrations in bone.
  • Sclerostin secreted by osteocytes helps negative feedback on osteoblasts’ bone deposition:
    • Differentially regulated based on mechanical loading, with decreased sclerostin in areas of concentrated strain.
    • Downregulation is associated with increased bone formation (via sclerostin antibody).
    • Potential for use in fracture healing, bone loss, implant osseous integration, and genetic bone diseases via upregulating sclerostin.

Osteoprogenitor cells:

  • Originate from mesenchymal stem cells.
  • It differentiate into different type of bone cells based on oxygen tension:
    • Become osteoblasts under conditions of low strain and increased oxygen tension
    • Become cartilage under conditions of intermediate strain and low oxygen tension.
    • Become fibrous tissue under conditions of high strain.

Bone Matrix:

  • Bone matrix consists of organic and Inorganic components.

Organic Components:

  • Forms 40 % of dry weight of the bone.
  1. Collagen:
    • Forms 90 % of organic components.
    • Primarily type I that provides tensile strength of bone.
  2. Proteoglycans:
    • Consist of glycosaminoglycan-protein complexes.
    • Provides compressive strength of the bone.
  3. Matrix proteins (noncollagenous):
    • Osteocalcin:
      • Inhibited by PTH and stimulated by 1,25-dihydroxyvitamin D3
      • Can be measured in serum or urine as a marker of bone turnover.
    • Osteonectin:
      • Secreted by platelets and osteoblasts
      • Have a role in regulating calcium or organizing mineral in matrix.
    • Osteopontin:
      • It’s a cell-binding protein.
  4. Growth factors and cytokines:
    • IL-1, IL-6, IGF, TGF-beta, BMPs

Inorganic Components:

  • Inorganic (mineral) components: forms up to 60% of dry weight of bone.
    • Calcium hydroxyapatite [Ca10(PO4)6(OH)2].
    • Calcium phosphate.

Bone Circulation

  • Bone receives 5% to 10% of the cardiac output.

Bone Circulation main supply comes from 3 main sources:

1. Nutrient artery system.

  • Branch from systemic arteries, enter the diaphyseal cortex through the nutrient foramen.
  • Blood supply to the inner two thirds of the mature diaphyseal cortex is via the haversian system.
  • Blood pressure (BP) in the nutrient artery system is high.
  • 60% of cortical bone vascularized by nutrient arteries

2. Metaphyseal-epiphyseal system

  • Arises from the periarticular vascular plexus.

3. Periosteal system

  • Consists mostly of capillaries that supply the outer third (at most) of the mature diaphyseal cortex.
  • Blood pressure in the periosteal system is low.

Direction of flow

  • Mature bone:
    • Arterial flow in is centrifugal (inside to outside).
      • Due to the high pressure nutrient artery system and the low pressure periosteal system.
    • When fracture disrupts the nutrient artery system, the periosteal system pressure predominates and blood flow is centripetal (outside to inside).
  • Immature developing bone:
    • Flow in is centripetal because the highly vascularized periosteal system is the predominant component.
  • Venous flow in mature bone is centripetal.
  • Cortical capillaries drain to venous sinusoids, which drain to the emissary venous system.