1. STRUCTURE, INJURY & HEALING
ARTICULARCARTILAGE
STRUCTURE, INJURY & HEALING
Nadhaporn Saengpetch
Division of Sports Medicine,
Department of Orthopaedics,
Faculty of Medicine Ramathibodi Hospital,
Mahidol University

2. COMPOSITION Extracellular matrix and sparse cells
No blood vessel, lymphatic vessel and nerve
limit response to any metabolic response
Frictionless

3. CHONDROCTYE
Endoplasmic reticulum and Golgi apparatus (matrix synthesis)
Intracytoplasmic filament, lipid, glycogen, secretary vesicles (maintenance of matrix structure)

4. CHONDROCYTE: DIFFERENT BY LAYERS
Surface layer: elongated and resemble fibroblasts
Transitional layer: round and actively for chemistry
Deeper layer:
cells in radial pattern
Tidemark:
non-functional cells

5. COLLAGEN FIBRILS

6. CHONDROCYTE: FUNCTION
NOT participate in water distribution
Maintenance and structural competence
Producing and replacing appropriate macromolecules (degradation, mechanical demand placed on the surface, synthesizing)
Assembling as an highly
ordered framework

7. CARTILAGE ZONES

8. EXTRACELLULAR MATRIX (ECM)
2 components
1. Tissue fluid
2. Framework of structural macromolecule
Interaction -> stiffness and resilience

9. ECM Water 80% by weight Gel forming = lubrication system
Large aggregation of Proteoglycans (maintain fluid within the matrix and e’lyte concentration)

10. ECM MOVEMENT
Cl-
Na+
Cl-
Na+
inorganic ion tissue osmolarity

11. STRUCTURAL MACROMOLECULES

12. STRUCTURAL MACROMOLECULES
Collagens
Proteoglycans
Noncollagenous proteins
20-40% wet wt.

13. COLLAGEN 60% of dry weight of cartilage Collagen-rich superficial zone
Types: II*, VI, IX, X and XI
Type II, IX and XI form the cross-band fibrils

14. TIGHT MESHWORK Collagen fibrils organization Large proteoglycans
Tensile stiffness & cartilage strength
Large proteoglycans
entrapment
Cohesiveness of tissue

15. TYPE II COLLAGEN 90-95% of cartilage collagen
The primary component of cross-banded fibrils

16. TYPE VI COLLAGEN Forms an important part of surrounding chondrocytes
Helps chondrocyte attach to matrix

17. TYPE IX COLLAGEN Bind covalently to superficial layers of cross-banded
fibrils
Project into the matrix to bind with other Type IX Collagen and Proteoglycans
Have GAG-> Proteoglycan?

18. TYPE X COLLAGEN TYPE XI COLLAGEN
Found only near cartilage calcified zone and hypertrophic zone of growth plate (start to mineralize)
Cartilage mineralization
Bind covalently to Type II
May form part of interior structure of cross-banded fibrils

19. PROTEOGLYCANS
A protein core & Glycosaminoglycans (GAG) chains (unbranched polysaccharide)
GAG: Hyaluronic acid, chondroitin sulfate, glucosamine sulfate, dermatan sulfate

21. AGGRECANS Mostly fill in the interfibrillar space of matrix
90% of Pg mass
Noncovalently bind with HA & monomer
Help anchor Pg in the matrix, prevent displacement during deformation, organize and stabilize Pg & collagen

22. DECORINS
One dermatan sulfate chain

23. BIGLYCAN & FIBROMODULIN
Two dermatan sulfate chains
Several dermatan sulfate chains
Biglycan
Fibromodulin

24. Healing
+ Degradative
enzymes
Transforming
growth factor β

25. HYALURONIC ACID Backbone for matrix aggregation
Bind aggrecans non-covalently and link proteins
This aggregation helps anchor Pg within the matrix
Prevent displacement during deformation
Stabilize relationships of Pg and collagen meshwork

26. NONCOLLAGENOUS PROTEINS & GLYCOPROTEINS
Stabilize the matrix framework
Help chondrocytes bind to the macromolecules of matrix
Anchorin CII collagen-binding chondrocytes surface protein (anchor)
Cartilage oligomeric protein (COMP) is in chondrocyte territorial matrix, have capacity to bind to chondrocyte

27. ZONES OF ARTICULAR CARTILAGE

28. SUPERFICIAL ZONE Thinnest zone Two sub layers:
sheet of fine fibrils (acellular)
flattened ellipsoid-shape chondrocyte + fibroblast
Collagen is lying parallel to the joint surface (resist compressive force)-> OA
High collagen, low Pg
“cartilage skin”

29. TRANSITIONAL ZONE Large volume cells: synthetic organelles (ER, Golgi)
spheroidal shape
Lower collagen & water concentration
Higher Pg concentration

30. MIDDLE(RADIAL/DEEP) ZONE
Chondrocytes align in columns perpendicular to the joint surface (resist shear stress)
Largest diameter collagen
Highest Pg
Lowest water
Collagen fibers pass into the tidemark

31. CALCIFIED CARTILAGE ZONE
Thin calcified cartilage
“calcific sepulchers”
Extremely low level of metabolic activity
No nutrients traverse this zone

32. MATRIX REGIONS Pericellular Territorial Interterritorial >>>
Bind cell membranes to matrix macromolecules
Protect deformation force
Transmit mechanical signals to chondrocytes
Provide the mechanical properties of tissue

33. CHONDROCYTE-MATRIX INTERACTIONS
Matrix protects chondrocytes from mechanical damage and maintain shape and phenotype
Matrix : metabolic products/cytokines and growth factors
Insulin-dependent growth factor I (IGF-I) & Transforming growth factor β (TGF β) + matrix synthesis & cell proliferation

34. CHONDROCYTE-MATRIX INTERACTIONS
IGF-I
TGF β +

35. BIOMECHANICS Wide range of static & dynamic mechanical loads
Tension
Compression
Shear
Wide range of static & dynamic mechanical loads
Compressive, tensile & shear forces
α composition & structure of ECM

36. TENSILE & SHEAR FORCE
These forces are resisted by rope-like collagen fibrils

37. COMPRESSIVE FORCE
Resisted by highly charged GAG such as aggrecan molecules

38. LOADING vs IMMOBILIZATION
Induced wide range of metabolic response
Decreased in matrix synthesis

39. CARTILAGE REGENERATION
Static compression
Reversibly inhibit cartilage matrix synthesis
Cyclical compressive
Stimulate aggrecan core protein & protein synthesis

40. DEGENERATION AND OSTEOARTHRITIS
Osteoarthritis >> degenerative joint disease, degenerative arthritis, hypertrophic arthritis

41. HOW THEY CHANGE?

42. OA: 3 OVERLAPPING PROCESSES
Cartilage matrix damage
Chondrocyte response to tissue damage
Decline of the chondrocyte synthetic response

43. STAGE 1 MATRIX DAMAGE Water Aggrecan & GAG length Permeability
& Matrix stiffness
Other causes: inflammation, tissue’s metabolic
changes that interferes matrix maintenance

44. STAGE 2 CHONDROCYTE RESPONSE
Chondrocytes detect tissue damage
Anabolic & mitogenic growth factors
chondrocyte proliferation & ECM +
Reversible
Spontaneous
Intervention
Catabolic enzymes (proteases)

45. STAGE 3 DECLINE CELL SYNTHESIS
Failure to restore the tissue
Progressive loss of cartilage
Down regulation of chondrocyte response to anabolic cytokine

46. JOINT INJURY & POSTTRAUMATIC OA
Ligament reconstruction (ex. ACL-R) can restore mechanical stability but not greatly reduce the risk for OA development because….
The initial traumatic event may have irreversible effects on the joint tissues and residents cells

47. Good Luck