Structural Cells, Bone and Cartilage Lecture Notes

Key Components of Connective Tissue

  • Connective tissue is one of the four primary tissue types.
  • It supports and holds the human body together.
  • Examples:
    • Cartilage
    • Bone
    • Adipose tissue (fat)
    • Fibrous connective tissues (tendons and ligaments)
    • Loose connective tissue
    • Blood (in some classifications)
  • This lecture focuses on cartilage and bone.

Components of Connective Tissues

  • All connective tissues have two main components:
    • Specialized cells
    • Extracellular matrix (ECM)
  • The extracellular matrix is composed of:
    • Fibers
    • Ground substance

Specialized Cells

  • Vary across different connective tissues:
    • Chondrocytes: cartilage
    • Osteocytes: bone
    • Adipocytes: fat
    • Fibroblasts: fibrous connective tissues
  • Specialized cells synthesize and secrete the ECM.

ECM Fibers

  • Secreted by specialized cells.
  • Include:
    • Collagen fibers
    • Elastin fibers
    • Reticular fibers

Ground Substance

  • Also secreted by cells.
  • Functions as a nutrient source.
  • Includes water, macromolecules, and proteoglycans.

Variability in Connective Tissues

  • The relative proportion and composition of cells, fibers, and ground substance varies.
  • This variation gives rise to different properties and functions.
  • Examples:
    • Blood: fluid-like
    • Fibrous connective tissues: dense fibers
    • Cartilage: gel-like
    • Bone: solid

Dominance of Extracellular Matrix

  • The ECM is typically the dominant component in connective tissues.
  • Cells are in the minority.
  • Mechanical and physical properties depend largely on the ECM composition.

Cartilage

Composition

  • Composed of chondrocytes.
  • Chondrocytes are embedded within an ECM rich in collagen fibers, proteoglycans, and glycosaminoglycans.
  • Avascular and neural: lacks nerves, blood vessels, and lymphatic vessels.

Types of Cartilage

  • Three types: hyaline, elastic, and fibrous.
  • All contain chondrocytes in a matrix, but the ECM composition varies, leading to different biomechanical properties.
Hyaline Cartilage
  • ECM is composed purely of collagen type II fibers.
  • Strong, flexible, and resists compression due to high tensile strength of collagen fibers.
Elastic Cartilage
  • Contains chondrocytes secreting collagen type II fibers and elastic fibers.
  • Strong, flexible, elastic, and resilient.
  • Elastic fibers are visible in histological sections.
Fibrous (Fibrocartilage) Cartilage
  • ECM contains both collagen type II and collagen type I fibers.
  • Extremely tough and resistant to compressive and load forces.

Location of Different Cartilage Types

  • Located in regions where strength, structural integrity, compression resistance, or flexibility are needed.
Hyaline Cartilage Locations
  • Most abundant type of cartilage.
    • Respiratory tract (trachea and bronchi): provides structural support to prevent airway collapse during breathing.
    • Articular surfaces of joints: protective layer for frictionless movement, degeneration leads to osteoarthritis.
    • Costal cartilage (ends of ribs).
    • Developing skeletal structures.
Elastic Cartilage Locations
  • External ear: allows bending and twisting.
  • Epiglottis: covers the trachea during swallowing.
Fibrocartilage Locations
  • Intervertebral discs: act as shock absorbers between vertebrae, with a gel-like center surrounded by layers of fibrocartilage.
  • Pubic symphysis.

Bone

Composition

  • Composed of osteocytes embedded in a calcified extracellular matrix.
  • Has a rich neurovascular supply.

Osteons

  • Cylindrical structures running along the length of long bones.
  • Composed of concentric layers of ECM with embedded osteocytes.
  • Central canal at the center of each osteon contains the neurovascular supply (arteries, veins, and nerves).
  • Arrangement ensures osteocytes are close to the neurovascular supply.

Extracellular Matrix of Bone

  • Composed of collagen fibers, other bone-unique proteins for calcification, macromolecules, and proteoglycans.
  • Uncalcified ECM is called osteoid.
  • Calcification occurs with the deposition of hydroxyapatite crystals (calcium phosphate) along collagen fibers, hardening the ECM.

Bone Cells

  • Osteocytes: most abundant (90-95% of cellular content).
  • Osteoblasts: bone builders
  • Osteoclasts: responsible for breakdown and resorption of bone.
Osteoblasts
  • Responsible for the formation of new bone tissue.
  • Synthesize and secrete uncalcified ECM (osteoid).
  • Regulate osteoid calcification by releasing calcium and phosphate ions to form hydroxyapatite crystals.
  • Become encased in the matrix and differentiate into osteocytes.
Osteocytes
  • Cells completely encased in bone matrix.
  • Involved in bone maintenance, regulating mineral and protein composition of bone matrix.
  • Form long cytoplasmic processes extending into the matrix to monitor composition and connect with neighboring osteocytes.
Osteoclasts
  • Large, multinucleated phagocytic cells.
  • Responsible for the breakdown and resorption of bone, secreting acids to break down hydroxyapatite crystals and enzymes to break down collagen fibers.

Function and Location of Bone

  • Provides structural support to the entire human body.
  • The adult skeleton is composed of 206 bones.
  • Divided into axial (bones along the body's axis) and appendicular (limb bones) skeletons.
  • Functions:
    • Surrounds and protects soft tissues and organs.
    • Acts as levers and muscle attachment points for movement.
    • Important storage site for minerals (calcium and phosphate).

Developmental Origins of Cartilage and Bone

Mesenchymal Cells

  • Specialized cells arise from mesenchymal cells.
  • Pluripotent stem cells that migrate through the developing embryo.
  • Differentiate into specialized cell types of connective tissues.

Mesenchymal Cell Lineages

  • Three distinct lineages give rise to cartilage and bone:
    • Paraxial mesoderm
    • Lateral plate mesoderm
    • Cranial neural crest cells
Paraxial Mesoderm
  • Undergoes mesenchymal to epithelial transition to form somites.
  • Somites divide into dermatomyotome and sclerotome.
  • Sclerotome cells undergo epithelial to mesenchymal transition.
  • Mesenchymal cells migrate and give rise to connective tissues of the axial skeleton (vertebral column, ribs, some craniofacial structures).
Lateral Plate Mesoderm
  • Gives rise to connective tissues of the appendicular skeleton (limbs).
  • Mesenchymal cells emerge at specific locations and proliferate to form limb buds.
  • FGF10FGF10 is an important signaling molecule expressed in the lateral plate mesoderm at future limb bud locations.
Cranial Neural Crest Cells
  • Derived from the neural tube during embryonic development.
  • Migrate into bronchial arches and give rise to mesenchymal cells.
  • Develop into craniofacial bones.

Chondrogenesis

  • The process by which cartilage is developed.
  • Key steps:
    • Mesenchymal stem cells migrate to specific regions.
    • Proliferate and express cell adhesion molecules (e.g., NCAM, N-cadherin).
    • Aggregate to form condensations of precartilaginous tissue.
    • Progenitor cells differentiate into chondrocytes.
    • Chondrocytes express genes to synthesize and secrete ECM.

Ossification

  • Process of bone formation.
  • Two types:
    • Intramembranous ossification
    • Endochondral ossification

Endochondral Ossification

  • Hyaline cartilage precursor is replaced with bone.
  • Example: Formation of long bones.
Long Bone Anatomy
  • Longer than they are wide (found a lot in limbs).
  • Epiphyses (ends of the bone).
  • Diaphysis (central shaft of the bone).
  • Medullary cavity (within the diaphysis, typically filled with bone marrow).
  • Articular cartilage (on the ends of the bone).
Process of Endochondral Ossification
  • Mesenchymal cells migrate, proliferate, and differentiate into chondrocytes, forming cartilage tissue.
  • Chondrocytes in the middle hypertrophy and undergo apoptosis.
  • Blood vessels invade, bringing osteoblasts (bone-building cells).
  • Primary ossification center forms in the middle of the cartilage matrix.
  • Ossification proceeds outward from the primary ossification center.
  • Secondary ossification centers form in the epiphyses.
  • Cartilage precursor is replaced with bone, leaving hyaline cartilage in the epiphysial growth plate and articular cartilage.
Histological Sections
  • Chondrocytes proliferate and are embedded in the ECM.
  • Chondrocytes begin to hypertrophy, increasing in size.
  • Hypertrophic chondrocytes secrete molecules causing the surrounding ECM to calcify.
  • Calcified matrix makes diffusion of nutrients difficult, leading to chondrocyte apoptosis.
  • Blood vessels invade, bringing hematopoietic cells and osteoblasts.
  • Calcified ECM acts as a scaffold for bone deposition.
Epiphyseal Plates
  • Hyaline cartilage persists throughout childhood and adolescence.
  • Proliferation and differentiation of chondrocytes within this plate drive longitudinal bone growth and elongation until adult height is achieved.
Zones of Epiphyseal Plates
  • Zone of resting or non-proliferative cartilage.
  • Proliferative zone: chondrocytes divide by mitosis and form longitudinal stacks.
  • Zone of hypertrophy: chondrocytes enlarge.
  • Zone of calcification: ECM surrounding chondrocytes calcifies.
  • Zone of ossification: bone deposition occurs.
  • In humans, longitudinal bone growth continues until pre-puberty. Increasing levels of oestrogen in both bio males and bio females will gradually slow down the growth of this epiphysial plate until eventually this cartilage is completely ossified and replaced with bone, at which point there will be no further longitudinal bone growth.
Defects in Epiphyseal Plate Development
  • Achondroplasia: mutations reduce chondrocyte proliferation, impairing bone elongation and causing a short limb phenotype.
  • Limb length discrepancies: limbs lengthen and grow at different rates, resulting from congenital birth defects or epiphyseal plate injuries.

Regenerative Capacity of Bone vs. Cartilage

  • Structural tissues are frequently damaged by injury or disease.
  • The body's response to these injuries can vary drastically depending on the type of connective tissue that has been injured.
  • Bone and cartilage have drastically different regenerative capacities, largely due to the different composition of these tissues that you learnt about at the start of the lecture.

Bone Regeneration

  • Has a remarkable potential for repair following injury.
  • Rich neurovascular supply.
  • Fractured bones lead to the formation of a blood clot or hematoma.
  • Mesenchymal stem cells are recruited to the damaged area and travel along blood vessels.
  • They proliferate and differentiate into fibroblasts, chondrocytes, and osteoblasts.
  • Fibroblasts and chondrocytes form a fibrocartilaginous callus.
  • Osteoblasts migrate and deposit osteoid, forming a bony callus.
  • The bony callus is remodeled by osteoblasts, osteoclasts, and osteocytes, leading to mature bone and a fully healed fracture.

Cartilage Regeneration

  • Has a very limited potential for repair following injury or disease.
  • Chondrocytes have limited migratory capacity because they are embedded in that collagen rich extracellular matrix.
  • Cartilage has no neurovascular supply. This limits it's capacity to be able to repair these injuries.
  • In instances where we do get some repair occurring, for example, sometimes we do see limited repair of damaged hyaline cartilage, that damaged hyaline cartilage is actually replaced with a different type of cartilage with fibra cartilage. Because this type of cartilage has drastically different properties, as you learnt about at the start of the lecture, it means that we're essentially taking our functional hyaline cartilage and we're then replacing it with scar tissue.
  • In instances where some repair does occur in hyaline carilage it is typically replaced with the the damaged hyaline carilage turns into fibra cartilage.
  • Because this type of cartilage has drastically different properties, as you learnt about at the start of the lecture, it means that we're essentially taking our functional hyaline cartilage and we're then replacing it with scar tissue.

Lecture Summary

  • Connective tissues are composed of specialised cells embedded in extracellular matrix, which is composed of fibres embedded in ground substance.
  • Cartilage is composed of chondrocytes embedded in collagen rich extracellular matrix.
  • There are three types of cartilage: hyaline, elastic and fibric cartilage. Each has a slightly different extracellular matrix, which gives these tissues slightly different biomechanical properties.
  • Bone is composed of several different specialised cells, including osteoblasts, osteocytes and osteoclasts. Bone has a really unique solid and calcified extracellular matrix.
  • Connective tissues arise from mesenchymal stem cells, and that there are three specific lineages of mesenchymal stem cells that give rise to our bone and cartilage structures within the body:
    • Paraxial mesoderm
    • Lateral plate mesoderms
    • Cranial neural crest cells
  • Chondrogenesis is the process of cartilage formation.
  • Ossification is the process of bone formation.
  • There are two different types of ossifications.
    • Intramembranous, which involves a mesenchymal precursor being replaced by bone.
    • Endochondral ossification, which involves a cartilage precursor being replaced by bone.