Microanatomy of Bone, Cartilage, Tendon, Ligament, and Joint - Comprehensive Notes

Skeletal System Functions

• Bone:

  • Provides frame and body structure.

  • Protects and supports soft tissues (e.g., brain).

  • Involved in hematopoietic tissue production.

  • Stores minerals.

• Cartilage:

  • Offers semi-rigid support to specific sites, found between bones, joints, ligaments, respiratory tree, and intervertebral discs.

  • Acts as a shock absorber in menisci and intervertebral discs.

  • Protects the ends of bones.

  • Three types: hyaline, elastic, and fibrocartilage.

• Ligaments:

  • Provide stability to joints; connect bone to bone.

• Tendons:

  • Provide strong, flexible connections between muscles and bones.

  • Important to consider in athletes and overweight patients due to potential strain.

• Joints:

  • Spaces with fluid between bones.

  • Lubricated, providing varying degrees of movement and flexibility.

Skeletal System Differentiation

• Originates from undifferentiated mesenchymal cells.

  • These cells can differentiate into various cell types like cartilage, bone, and fibrous tissue.

Bone Composition and Remodeling

• Bone is a dynamic, living tissue constantly being remodeled.

  • Osteoid:

    • Composed of 90% collagen and inorganic (mineral) components.

    • Hydroxyapatite: $\text{Ca}<em>{10}(\text{PO}</em>4)<em>6(\text{OH})</em>2$ is a key mineral component.

Bone as an Organ

• Bones are organs.

  • Protect other organs (e.g., brain).

  • Produce hematopoietic cells.

  • Store minerals.

  • Provide structure and support.

  • Lightweight yet strong, with internal flexibility from spongy bone.

Types of Bone

• Trabecular Bone (T):

  • Also known as cancellous or spongy bone.

  • Large surface area; contains bone marrow.

• Cortical Bone (C):

  • Also known as compact bone.

  • More dense than trabecular bone.

• Bone Regions:

  • E - Epiphysis

  • D - Diaphysis

  • M - Metaphysis

  • P - Physis = Growth Plate

  • AC - Articular Cartilage

Bird Bones

• Pneumatic: Rarefied trabecular bone with broader spaces.

Adult Long Bone structure

• Articular cartilage.

• Epiphysis.

• Cancellous bone.

• Compact bone.

• Medullary cavity containing yellow marrow.

• Periosteum.

• Endosteum.

• Epiphyseal lines.

• Secondary epiphysis.

• Diaphysis.

Types of Mature and Immature Bone

• Mature Lamellar Bone:

  • Hard and strong.

  • Collagen in parallel layers.

  • Found in trabeculae and cortical bone.

• Woven Bone:

  • Soft and weak.

  • Disorganized collagen.

  • Indicates new bone formation.

  • Locations: fracture repair, inflammation, neoplasia.

Lamellar vs. Woven Bone

• Lamellar Bone:

  • Strong, mature bone that forms slowly.

  • Collagen fibers are arranged in layers (lamellae).

  • Organized into osteons (Haversian systems) in mature cortical and trabecular bone.

• Woven Bone:

  • Weak, immature bone produced quickly.

  • Disorganized arrangement of collagen fibers.

  • Present at sites of rapid bone formation (e.g., fracture repair, inflammation, neoplasia).

  • Can be remodeled into lamellar bone.

Osteon Structure

• Osteon: The functional unit of lamellar bone, arranged in circles around the central canal (Haversian canal) and in the interstitial bone between the circles of bone.

• Haversian canals: Seen at the center of each osteon.

• Volkmann's canals: Run in bone and connect Haversian (central) canals.

Haversian System

• Haversian Canals: Thin channels running between lacunae.

• Osteon: Circles of lamellar bone around a central canal.

• Lacunae: Small holes containing osteocytes.

Cellular Elements of Bone Tissue

• Osteoblasts: Derived from osteoprogenitor cells.

• Osteocytes.

• Bone lining cells.

• Osteoclasts: Monocytic origin.

Bone Cells and Their Functions

• Osteoblasts:

  • Produce osteoid (organic component of bone matrix) and initiate its mineralization.

  • Some become embedded in the bone and differentiate into osteocytes.

• Osteocytes:

  • Most abundant cells in bone.

  • Reside in lacunae surrounded by mineralized matrix.

• Osteoclasts:

  • Reside in shallow pits (Howship’s lacunae).

  • Bone resorption.

Bone Cell Characteristics

• Osteoblasts: Rounded, form a single row of cells along trabeculae.

• Osteocytes: Thinner and located within lacunae embedded in bone.

• Osteoclasts: Multinucleated cells located along trabeculae, resorb bone under stimulation of cytokines secreted by osteoblasts or inflammatory cells.

Bone Cells and Their Function

• Osteoblasts:

  • Osteoid formation.

  • Secrete Type I collagen.

  • Regulate mineralization.

  • Differentiate to become osteocytes.

  • Have receptors for PTH.

• Osteocytes:

  • Maintain bone matrix.

  • Occupy lacunae inside bone.

  • Extend filopodia through canaliculi that mobilize $\text{Ca}^{++}$.

• Osteoclasts:

  • Digest bone and play a crucial role in $\text{Ca}^{++}$ homeostasis.

  • Large multi-nucleated cells with ruffled border and clear zone.

  • Originate from stem cells of bone marrow (monocyte origin).

• Bone Lining Cells:

  • Flat, elongated cells.

  • Cover endosteal surfaces of inactive bone (bone undergoing neither formation nor resorption).

Hormonal Influence on Bone Metabolism

• Parathyroid Hormone (PTH): Promotes bone resorption.

• 1,25-Dihydroxyvitamin D3: Required for normal bone growth and mineralization; stimulates bone resorption.

• Calcitonin: Inhibits bone resorption.

• Glucocorticoids: Inhibit bone formation and stimulate resorption.

• Estrogen: Inhibits bone resorption.

• Insulin, growth hormone, androgens, and thyroid hormones are also involved in bone metabolism.

Bone Matrix

• Osteoid (organic component) contains:

  • Type I collagen: main component of osteoid (~90%).

  • Osteonectin: involved in mineralization.

  • Osteocalcin: vitamin K-dependent, also involved in mineralization.

  • Proteoglycans.

  • Growth factors (e.g., BMPs, IGFs, TGFs, FGFs).

• Hydroxyapatite $\text{Ca[10](PO[4])[6](OH)[2]}$ (inorganic component): needle-like crystals.

Bone Formation and Resorption

• Unmineralized bone (osteoid) is blue, produced by osteoblasts.

• Mineralized bone is black (special prep).

• Osteoclasts remove only mineralized bone.

• The processes of formation and resorption are coupled.

• When the processes are uncoupled, disease occurs.

Bone Development

• Intramembranous Ossification: ↑ WIDTH; adult

  • Bone formed from mesenchymal tissue in periosteum.

  • Occurs in flat bones of skull and pelvis and on all periosteal surfaces throughout life.

  • Responsible for the growth of bones in width.

  • No cartilage needed first

• Endochondral Ossification: ↑ LENGTH; young

  • Bone formed from hyaline cartilage precursors in physes.

  • Most bones develop by this method (appendicular, axial and base of skull).

  • Occurs at physes, responsible for the growth of bones in length.

  • Hyaline cartilage precedes and is scaffold.

Processes of Ossification

• Intramembranous Ossification:

  • Increases bone width.

  • Occurs in the periosteum.

  • Does not require cartilage.

• Endochondral Ossification:

  • Increases bone length.

  • Occurs at the physis (growth plate).

Stages of Endochondral Ossification

• Early cartilage model.

• Formation of primary ossification center, bony collar, and periosteum.

• Vascular invasion, formation of primary marrow cavity, and appearance of secondary ossification center.

• Bone at birth, with enlarged primary marrow cavity and appearance of secondary marrow cavity in one epiphysis.

• Bone of child, with epiphyseal plate at distal end.

• Adult bone with a single marrow cavity and closed epiphyseal plate.

Location

• Metaphysis (M), physis (P arrow) and epiphysis (E) distal femur

• Easy to see spongy/trabecular bone and the spaces between trabeculae which contain hematopoietic cells. Endochondral osteogenesis occurs at the physis.

Endochondral Bone Formation

• Growth plate = Physis (P)

• Endochondral bone formation is preceded by hyaline cartilage.

• It occurs in physes when cartilage differentiates, matures, mineralizes, dies, and is a scaffold that osteoblasts reside on.

• Osteoblasts produce osteoid on top of the spicules of cartilage.

• The cartilage is gradually remodeled and mineralized into mature lamellar bone

Growth Plate

• Growth plate = Physis

  • 1 - Zone of reserve/resting cells.

  • 2 - Zone of proliferation.

  • 3 - Zone of hypertrophic cells.

  • B – Primary spongiosa – bone forms on dead mineralized cartilage “scaffold”.

Bone Blood Supply

• Blood enters the marrow cavity of bones through nutrient, metaphyseal, and epiphyseal arteries.

• In young animals, the cortex is supplied mainly from the endosteal surface and exits via periosteal veins (i.e., blood flows centrifugally).

• With age, the cortex becomes increasingly dependent on periosteal arteries.

Cartilage

• Semi-rigid support to specific sites, present in many locations between bones, joints, ligaments, respiratory tree, and intervertebral discs.

• Acts as a shock absorber in menisci and intervertebral disks – Protects the ends of bones.

• There are three types of cartilage: hyaline, elastic, and fibrocartilage.

Cartilage Differentiation and Maturation

• Differentiation and maturation is most advanced at the center of a mass of growing cartilage; immature at the periphery (perichondrium).

• On completion of growth, the cartilage mass consists of chondrocytes embedded in a large amount of extracellular matrix.

• At the periphery of mature cartilage, there is a zone of condensed connective tissue (perichondrium), containing elongated fusiform cells that resemble fibroblasts.

• These cells give rise to chondroblasts.

Cartilage Characteristics

• Avascular semi-rigid form of connective tissue characterized by the absence of blood vessels, lymphatic vessels, and nerves (adults) – young animals have blood vessels in growing cartilage.

• Supports soft tissues (e.g., ear, eyelid, trachea, and bronchi).

• Very important for LONGITUDINAL bone growth – Endochondral ossification.

• Composed of cells (chondrocytes) that are embedded in an amorphous gel-like substance and connective tissue fibers, making this tissue resilient.

Chondrogenesis

• Embryonic mesenchyme.

• Proliferation and early differentiation.

• Chondroblasts separate from each other due to the production of matrix.

• Multiplication of cartilage cells in aggregates.

• Mature cartilage has slow cell turnover and replacement of cells.

Isogenous Group

• Cluster of chondrocytes formed through the division of a progenitor cell; found in hyaline cartilage, elastic cartilage, and fibrocartilage.

Cartilage & Bone Differentiation

• Endochondral ossification- cartilage in physes matures, dies, mineralized and forms scaffold to form bone – longitudinal growth of bones

Types of Cartilage

• Hyaline cartilage

• Elastic cartilage

• Fibrocartilage

Location of Cartilage

• Hyaline: Joints - articular cartilage, Ribs, Physes, Nose

• Elastic: Ear, Epiglottis

• Fibrocartilage: Menisci - Discs - Insertions of tendons & ligaments

Locations of Hyaline Cartilage

• Growth plates

• Articular cartilage covers joint surfaces at costo-chondral junctions of the ribs, the nasal septum, larynx, tracheal rings, and bronchi.

• Fetal axial and appendicular skeleton abundant type of cartilage.

Elastic Cartilage

• Has a perichondrium, chondroblasts, and chondrocytes in large lacunae.

• Contains abundant elastic fibers that stain darkly by specific dyes/stains.

• Flexible tissue due to the presence of numerous bundles of branching elastic fibers in the cartilage matrix.

• Found in the epiglottis and the corniculate and cuneiform processes of the arytenoid cartilage, in the external auditory canal, and in the ear pinna.

Fibrocartilage

• Lacks a perichondrium, thus does not have the capacity to regenerate.

• Fibrocartilage contains chondrocytes & lacunae. Features are intermediate between cartilage and dense fibrous connective tissue.

• Contains Type 1 collagen fibers.

• Located where support and tensile strength are required: Intervertebral discs (annulus fibrosus), menisci, insertions of tendons and ligaments, mandibular symphysis, pubic symphysis.

Locations of Fibrocartilage

• Intervertebral discs = annulus fibrosus, menisci, insertions of tendons, ligaments, mandibular symphysis, pubic symphysis.

Perichondrium

• The outer layer is composed of dense fibrous connective tissue; resembles mature fibroblasts.

• The inner layer is cellular and it is present in all hyaline cartilage except on articular surfaces.

• Inner layer is chondrogenic, contains cells with the capacity to become chondroblasts (i.e., can regenerate) BUT not present in articular cartilage.

Cartilage Matrix

• Components include collagen, elastic fibers, and proteoglycans (GAGs).

• Basophilia of cartilage matrix is due to the high concentration of GAGs.

• The matrix near the clusters of chondrocytes (territorial) is more basophilic due to the greater amount of GAG than the matrix further away from the chondrocytes (interterritorial).

GAGs

• GAGs = Sulfated polysaccharide units.

• Examples of GAGs include chondroitin sulfate, keratan sulfate, dermatan sulfate, heparan sulfate, and hyaluronan (hyaluronic acid in joint fluid).

• GAGs bound to a protein core form macromolecules called proteoglycans that are responsible for the strong and flexible property of cartilage – shock absorption.

• Within the matrix, GAGs are embedded at varying proportions of collagen and elastic fibers, giving rise to the different types of cartilage: hyaline, elastic, and fibro-cartilage.

Tendons and Ligaments

• Tendon muscle to bone

• Ligament bone to bone

• Function: attachments, flexibility

Tendon Composition

• Parallel bundles of type I collagen fibers in a tendon.

• Approximately 85% collagen (98% type I), 2% elastin, 1–5% proteoglycans.

Tendon Characteristics

• Tendon is primarily type I collagen, elastic, and strong.

• Mature tendon contains cells that have a limited ability to regenerate.

• Following injury, a tendon lays down type III collagen, or scar tissue, which is stronger than type I but stiffer and less elastic.

• This makes it less flexible and prone to re-injure when the animal begins to stretch the tendon during strenuous work.

Types of Joints

• Fibrous Joints (Synarthroses):

  • Bones or cartilages are united by fibrous tissue.

    • Sutures (cranial suture)

    • Syndesmosis (tibia-fibula)

    • Gomphosis (i.e., a tooth socket)

• Cartilaginous (Amphiarthrosis):

  • Bones or cartilages united by hyaline cartilage (i.e., costochondral joints) or fibrocartilage (i.e., pelvic and mandibular symphysis).

• Synovial (Diarthrosis/True joints):

  • Unite two bone ends and are covered by articular cartilage and surrounded by a thick articular capsule (i.e., synovial joints of appendicular skeleton and vertebral joints).

Joint Structure

• Morphologic Types of Joints:

  • Fibrous (synarthrosis) i.e. sutures in skull.

  • Cartilaginous (amphiarthrosis) i.e. ribs.

  • Synovial (diarthrosis) i.e. limbs.

Components in the Joint Cavity

• Bonesurfacesin the jointcavityare coveredbyhyaline cartilage (articular cartilage).

• The joint cavity consists of a capsule composed of a fibrous portion and a well vascularized synovial membrane lined by two types of cells:

  • Type A cell: phagocytic function – remove debris.

  • Type B cell: secrete hyaluronic acid, & protein complex (mucin) into synovial fluid = lubricant, protectant and nutrition to joints.

Articular Cartilage and Capsule

• Articular cartilage:

  • Surface should be smooth; formed by Type II collagen and proteoglycans; lacks blood vessels and nerves (poor capacity for regeneration).

  • Firmly attached to subchondral bone. Limited capacity for repair (nourishment comes from synovial fluid).

• Articular capsule:

  • Thick sac of connective tissue that covers the entire joint and provides additional joint stability.

Synovial Membrane and Fluid

• Synovial membrane:

  • Thin membrane with lots of villi superficially lined by a continuous layer of specialized cells (synoviocytes – type A are phagocytic; type B produce synovial fluid).

• Synovial fluid:

  • Clear, viscous, colorless or slightly yellow fluid produced by synoviocytes (low cellularity and low protein content).

  • Function is to reduce friction.

Terms to Know - Bone

• Osteocytes

• Osteoclasts

• Osteoblasts

• PTH

• Calcitonin

• Osteoid

• Spongy/cancellous/trabecular bone

• Compact/cortical bone

• Epiphysis, Diaphysis, Metaphysis, Physis

• Periosteum, Endosteum

• Lamellar bone vs woven bone

• Osteon

• Haversian canal

• Hydroxyapatite

• Howship’s lacunae

• Endochondral vs Intramembranous bone formation

• Nutrient, epiphyseal, metaphyseal arteries

• Bone blood supply

Terms to Know: Cartilage and Ligaments

• Hyaline, Elastic and Fibrocartilage

• Ligament vs Tendon

• Endochondral ossification

• Mesenchyme

• Chrondroblast

• Perichondrium

• Isogenous group

• Growth plate components (zone of reserve/resting cells, zone of proliferation, zone of hypertrophic cells, primary spongiosa)

• Metaphysis, physis, epiphysis

• Proteoglycans

• Tendinocyte/Tendon Fascicle

• Type I vs Type II collagen

• Synarthroses, Cartilaginous, and Synovial Joints

• Type A cell and Type B cell (synoviocytes)

• Synovial fluid