Bone and Cartilage Histology, Collagen

Courtesy: Amr Abdelgawad, Maimonaides Medical Centre, NY, USA

1. Types of Bone Histology

 

Organized Bone (Lamellar Bone)

 

Cortical Bone

– Forms the cortex of long bones.

– Located in the shaft of bones such as the femur and tibia.

– Dense with low porosity.

– Lower surface area for the same bone volume.

– Stronger and stiffer.

– Lower metabolic activity.

 

Cancellous Bone (Trabecular Bone)

– Located mainly in the metaphysis of long bones.

– Highly porous.

– Larger surface area.

– Less stiff compared to cortical bone.

– Higher metabolic activity.

 

Woven Bone

– Disorganized bone structure.

– Seen during early fracture healing and callus formation.

 

2. Bone Structure and Chemistry

 

Inorganic (Mineral) Component

– Makes up about 60–70 percent of bone.

– Mainly calcium and phosphate.

– Present primarily as hydroxyapatite crystals.

– Chemical composition: Calcium10(PO4)6(OH)2.

 

Organic Matrix

– About 30 percent of bone.

– Mainly composed of Type I collagen.

– Type I collagen accounts for about 90 percent of the organic matrix.

 

Water

– Approximately 5–8 percent of bone.

 

3. Bone Cells

 

Osteoclast

– Responsible for bone resorption.

– Derived from hematopoietic lineage.

– Develop from monocyte–macrophage cells.

– Multinucleated giant cells with ruffled border and sealing zone.

– Carbonic anhydrase generates hydrogen ions to dissolve mineral.

– Cathepsin and matrix metalloproteinases degrade organic matrix.

 

RANK–RANKL–OPG Pathway

– RANK present on osteoclast precursors.

– RANK ligand produced by osteoblasts.

– Interaction increases osteoclast formation and bone resorption.

– Osteoprotegerin blocks RANK ligand and reduces osteoclast formation.

– Denosumab acts similarly by blocking RANK ligand.

 

Factors Increasing RANK Ligand

– Interleukin 1

– Corticosteroids

– Vitamin D

– Continuous hyperparathyroidism

 

Osteoblast

– Derived from mesenchymal stem cells.

– Responsible for bone formation and matrix production.

– Produces osteocalcin.

– Osteocalcin is vitamin K dependent and produced only by mature osteoblasts.

– Major non collagenous protein in mature bone.

– Marker of bone formation.

 

Important Gene

– RUNX2 (CBFA1)

– Controls differentiation of mesenchymal stem cells into osteoblasts.

– Mutation leads to cleidocranial dysplasia.

 

Osteocyte

– Derived from osteoblasts embedded in bone matrix.

– Less metabolically active.

– Communicate through canaliculi.

– Sense mechanical stress and regulate remodeling.

 

4. Growth Plate (Physis)

 

Responsible for longitudinal growth of long bones.

Present only in growing skeleton.

 

Zones

 

Resting Zone

– Small chondrocytes.

– Large extracellular matrix.

– Low oxygen and metabolic activity.

 

Proliferative Zone

– Rapid chondrocyte division.

– Cells arranged in columns.

– High extracellular matrix synthesis.

 

Hypertrophic Zone

– Chondrocytes enlarge.

– Subdivided into maturation, degeneration, and provisional calcification.

 

Most physeal fractures occur in the zone of provisional calcification.

 

Supporting Structures

 

Perichondral Ring of LaCroix

– Provides mechanical support.

 

Groove of Ranvier

– Responsible for appositional growth.

 

5. Collagen

 

– Triple helical protein structure.

– Three alpha chains.

– Sequence pattern Glycine–X–Y.

– X and Y commonly proline or hydroxyproline.

 

Types of Collagen

 

Type I

– Main collagen in bone.

– Also present in skin and annulus fibrosus.

 

Type II

– Main collagen in cartilage.

 

Type IX and XI

– Minor collagen types in cartilage.

 

Type X

– Present in hypertrophic chondrocytes during endochondral ossification.

 

6. Articular Cartilage

 

Cells

– Chondrocytes (about 2 percent).

 

Extracellular Matrix

– About 98 percent.

– Components: water, Type II collagen, proteoglycans.

 

7. Layers of Articular Cartilage

 

Superficial Zone

– 10–15 percent thickness.

– Collagen parallel to surface.

– Highest tensile strength.

– Highest water and collagen content.

– Lowest proteoglycan.

 

Middle Zone

– Transitional layer.

 

Deep Zone

– Collagen perpendicular to surface.

– Highest proteoglycan content.

– Cells arranged in columns.

 

Calcified Zone

– Anchors cartilage to subchondral bone.

– Separated from deep zone by tidemark.

 

8. Glycosaminoglycans and Proteoglycans

 

Glycosaminoglycans

– Linear polysaccharides.

– Examples: chondroitin sulfate, keratan sulfate.

 

Proteoglycan Monomer

– Core protein attached to glycosaminoglycan chains.

 

Proteoglycan Aggregate

– Multiple monomers attached to hyaluronic acid via link proteins.

 

Function

– Bind water and provide resistance to compression.

 

9. Chondroprotective Factors

 

– Transforming growth factor beta

– Bone morphogenetic proteins 2 and 7

– Insulin like growth factor

– Glucosamine

 

Effects

– Increase collagen and proteoglycan synthesis.

 

10. Cartilage Degrading Factors

 

– Interleukin 1

– Tumor necrosis factor

– Matrix metalloproteinases

– Cyclooxygenase enzymes

 

Effects

– Increase cartilage degradation.

– Decrease proteoglycan synthesis.

 

11. Aging vs Osteoarthritis Changes

 

Aging

– Decreased water content.

– Increased stiffness.

– Decreased proteoglycan synthesis.

– Decreased chondrocyte number.

 

Osteoarthritis

– Increased water content.

– Softer cartilage.

– Increased proteoglycan turnover.

– Increased chondrocyte number.

 

12. Synovial Joint

 

Synovium Layers

– Intimal layer

– Subintimal connective tissue layer

 

Cell Types

 

Type A Cells

– Macrophage-like

– Phagocytosis

 

Type B Cells

– Fibroblast-like

– Produce synovial fluid

 

Synovial Fluid

– Contains hyaluronic acid

– Low protein concentration

– Non-Newtonian fluid behavior

 

13. Joint Lubrication

 

Elastohydrodynamic Lubrication

– Deformation of surfaces with fluid film lubrication.

 

Boundary Lubrication

– Occurs when fluid film is minimal.

– Lubrication via surface molecules.

 

14. Lubricin and Superficial Zone Protein

 

– Glycoproteins produced by superficial zone chondrocytes.

– Important for boundary lubrication.

– Hyaluronic acid interacts with lubricin to reduce friction.