bond

Maya Kiladze, PhD

Bone Definition

• Bone is a specialized connective tissue characterized by an extremely hard mineralized (calcified) extracellular matrix.

Functions of Bone

• Support and Protection: Provide structural support and protect vital organs in the body.

• Bone Marrow Cavities: Houses cavities that contain bone marrow, which is responsible for the formation of blood cells.

• Reservoir for Ions: Acts as a storage reservoir for calcium, phosphate, and other essential ions.

• Lever System: Functions as a system of levers that amplify the forces produced during skeletal muscle contraction, transforming these forces into bodily movements.

Properties of Bone

• Due to its hardness, bone cannot be sectioned routinely.

• The bone matrix can be softened by immersion in a decalcifying solution, preserving the shape of the bone, making it flexible,

• After decalcification, the bone can be subjected to fixation and embedding in paraffin for microtome sectioning.

• Types of Bone:
    - Compact (Cortical) Bone: Dense area near the surface constituting 80% of total bone mass.
    - Trabecular (Cancellous or Spongy) Bone: Deeper areas with interconnecting cavities, accounting for approximately 20% of total bone mass.
  

Components of Bone

• Bone Matrix: Composed of calcified extracellular material, lined by layers of connective tissue.
    - Types of Bone Cells:
      - Osteoprogenitor Cells: Stem cells that differentiate into osteoblasts.
      - Osteoblasts: Cells responsible for synthesizing bone matrix components.
      - Bone-Lining Cells: Covering cells that maintain the bone surface.
      - Osteocytes: Mature bone cells located in lacunae between matrix layers, with cytoplasmic processes extending into canaliculi.
      - Osteoclasts: Large cells responsible for bone resorption.
  

Nomenclature

• Prefix Meanings:
    - Osteo = bone
    - Chondro = cartilage
    - Peri = peripheral
    - Endo = inner lining

• Suffix Meanings:
    - Blast = precursor (secretes matrix)
    - Cyte = mature cell
  

Structure of Bone

• Most bone in adults, whether compact or spongy, is organized as lamellar bone characterized by multiple layers (lamellae) of calcified matrix.
    - Osteocytes reside in individual lacunae and receive nutrients from microvasculature through canaliculi.

Periosteum

• Outer Layer: Composed of dense connective tissue containing blood vessels, collagen fibers, and fibroblasts.

• Inner Layer: Contains bone lining cells, osteoblasts, and osteoprogenitor cells.

• Vascularization: Bone is vascularized by vessels originating from the periosteum and penetrating the matrix through transverse perforating (Volkmann) canals.

• Sharpey Fibers: Collagen fibers binding the periosteum to the bone.

Endosteum

• A thin connective layer covering all trabeculae around marrow cavities, containing osteoprogenitor cells, osteoblasts, bone lining cells, and osteoclasts.

Osteon (Haversian System)

• An osteon consists of concentric lamellae surrounding a central canal that contains blood vessels and nerves.

• Lacunae, housing osteocytes, are distributed between lamellae, interconnected by canaliculi with cellular processes.

• Adjacent cells communicate via gap junctions.

Bone Cells Developmental Pathways

• All bone cells (except osteoclasts) originate from mesenchymal stem cells which differentiate into different cell types as follows:
    - Osteoprogenitor Cells
    - Osteoblasts
    - Bone-Lining Cells
    - Osteocytes
    - Osteoclasts: Originate from hemopoietic progenitor cells, responsible for bone resorption.

Osteoblasts

• Function: Osteoblasts synthesize bone matrix components.
    - Components Synthesized:
      - Type I collagen fibers
      - Proteoglycans
      - Several glycoproteins

• Characteristics:
    - Active osteoblasts: Cuboidal shape and basophilic (blue-staining) cytoplasm.
    - Inactive osteoblasts: Flattened bone lining cells with less basophilia.

• Osteoid Production: Osteoblasts produce a layer of new (non-calcified) material, called osteoid, between their layer and the pre-existing bone surface.

Osteocytes

• Definition: Mature bone cells enclosed within the bone matrix.

• Functions:
    - Maintaining the bone matrix.
    - Mechanotransduction - osteocytes respond to mechanical stresses applied to the bone.
    - Participation in matrix degradation.

• Illustrations:
    - Transmission Electron Microscopy (TEM) showing an osteocyte in a lacuna and its processes within canaliculi.

Bone-Lining Cells

• Derived from osteoblasts, these cells cover unremodeled bone.

• Types of Bone-Lining Cells:
    - Periosteal Cells: On external surfaces.
    - Endosteal Cells: On internal surfaces.

• Function: Maintain and support osteocytes, regulating calcium and phosphate movement in and out of the bone.

Osteoclasts

• Characteristics:
    - Large, multinucleated cells responsible for bone resorption.
    - Can create resorption bays (Howship's lacunae) beneath them.

• Distinctive Features:
    - Large size
    - Multinucleation
    - Acidophilia (staining brightly in acidic environments).

• Development: Derived from the fusion of monocytes.

Bone Matrix Composition

• Inorganic Material: Comprises 55% of dry weight, including:
    - Calcium hydroxyapatite (most abundant)
    - Bicarbonate, citrate, magnesium ions, potassium ions, sodium ions.

• Organic Material: 30%, includes:
    - Type I collagen
    - Proteoglycan aggregates
    - Bone-specific multiadhesive glycoproteins.

• Water: 15%, facilitates ion exchange between the mineral and body fluids.

Immature vs. Mature Bone

• Immature Bone:
    - Lacks organized lamellar structure.
    - Higher cellularity and lower mineral content compared to mature bone.

• Mature Bone:
    - Organized in lamellar structure with cells arranged in a circular pattern reflecting the osteonal organization.

Osteogenesis (Bone Development)

• Occurs by two processes:
    - Intramembranous Ossification:
      - Osteoblasts differentiate from mesenchyme, begin osteoid production. Primarily forms bones of the skull, jaws, scapula, and clavicle.
    - Endochondral Ossification:
      - Pre-existing hyaline cartilage matrix is invaded by osteoblasts that then produce osteoid. Happens in all other bones.

• Both processes first produce temporary woven bone, quickly replaced by stronger lamellar bone.

Phases of Intramembranous Ossification

• Groups of mesenchymal cells differentiate as osteoblasts, producing osteoid.

• Osteocytes form as cells get trapped in the calcifying matrix.

• Woven bone is vascularized, developing periosteum covers it.

• Remodeling leads to compact lamellar bone layers surrounding spongy bone.

Phases of Endochondral Ossification

1. Fetal hyaline cartilage model develops.

2. Cartilage calcifies, and a periosteal bone collar forms around diaphysis.

3. Primary ossification center emerges in the diaphysis.

4. Secondary ossification centers appear in epiphyses.

5. Bone replaces cartilage (articular and epiphyseal plates remain).

6. Epiphyseal plates ossify, forming epiphyseal lines.

Growth of Bones

• Lengthening: Achieved through chondrocyte proliferation in the epiphyseal plate, which displaces it away from the diaphysis, maintaining thickness.

• Thickness Growth: Occurs via osteoblast and osteoclast activity in response to stress, termed appositional growth.

Bone Repair Mechanism

• Bone has significant repair capacity due to osteoprogenitor stem cells and rich vascularization.

• Fracture Healing Process:
    - Torn blood vessels lead to a clot (fracture hematoma).
    - Hematoma is cleaned up by macrophages, replaced by fibrocartilage mass (procallus) rich in collagen and fibroblasts.
    - If the periosteum is broken, it reestablishes continuity.
    - The procallus is invaded by blood vessels and osteoblasts, gradually replaced by trabecular woven bone, forming a hard callus.
    - The woven bone remodels to form compact and cancellous bone, restoring functional blood supply.

Suggested Study Material

• Junqueira's Basic Histology: Chapter 8, pages 138 - 160