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

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

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

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

COLLAGEN FIBRILS

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

CARTILAGE ZONES

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

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

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

STRUCTURAL MACROMOLECULES

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

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

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

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

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

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?

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

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

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

DECORINS One dermatan sulfate chain

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

Healing + Degradative enzymes Transforming growth factor β

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

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

ZONES OF ARTICULAR CARTILAGE

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”

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

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

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

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

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

CHONDROCYTE-MATRIX INTERACTIONS IGF-I TGF β +

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

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

COMPRESSIVE FORCE Resisted by highly charged GAG such as aggrecan molecules

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

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

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

HOW THEY CHANGE?

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

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

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

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

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

Good Luck