Alphonsus Chong's Personal Wiki

Cells (chondrocytes) - 5%

ECM

- Fibers

1. Collagen Type II (10-20%)
2. Other collagens IX, XI, VI, X

-Elastins Ground substance

- H20 (75%) - Proteoglycans and glycosaminoglycans

1. aggrecan
2. Hyaluronan
3. Decorin, byglycan, fibromodulin, syndecan, lumican, superficial zone protein

- Glycoproteins

1. Cartilage oligomeric protein (COMP), laminin, lubricin, chondro-adherin
2. Cartilage matrix protein (CMP), cartilage matrix glycoprotein (CMGP), chondronectin, fibronectin, anchorin CII

- Degradative enzymes (matrix metalloproteinases) - Extracellular ions

Structure

Layers

- decreasing H20, collagen, increasing PG from superficial to deep - I Superficial gliding zone: thinnest, collagen fibers parallel to resist shear; first to show OA - II Middle transitional zone: fibers obliquely; II and III have chondrons: communities of 2-3 chondrocytes - III radial zone: largest, resists load and distributes compression - tidemark - acellular; boundary between calcified and uncalcified cartilage - IV calcified zone: hydroxyapatite crystals, type X collagen

Collagen

- 90% type II - Type I not normally found, only following injury - Type X: associated with cartilage calcification

Proteoglycans and glycosaminoglycans

- responsible for most of the water content of cartilage - gives compressive strength - hydrophilic molecules - GAG (chondroitin sulphate, keratan sulphate) bound by sugar bonds to linear core of protein - Aggrecan is the predominant proteoglycan

Degradative Enzymes

- Matrix metalloproteinases

1. collagenases
2. stromelysins
3. gelatinases
4. membrane-associated metalloproteinases

- Tissue-induced metalloproteinase inhibitors (TIMPs)

1. acidic polypeptides
2. maintains avascular nature of cartilage

Ions

- high sodium and potassium ion - sulphate residues on PGs attract these ions - calcium high in calcified zone

Glycoproteins

- macromolecules: tissue glue - COMP –> binds to various matrix proteins - lubricin - joint lubricant

Chondrocytes

- from MSCs - articular and growth plate chondrocytes –> different terminal differentiation - diffusion for cell nutrition - joint loading important for nutrition

Function

- joint lubrication

1. low coefficient of friction (0.002), 30 x « joint replacements
2. lowered by fluid-film deformation, elastic deformation of articular cartilage, synovial fluid and efflux of fluid from cartilage

- shock absorption

1. 10x » bone
2. diffuses load

Biomechanical properties - creep - sress relaxation - anisotropic

Lubrication

- boundary lubrication - fluid film lubrication

1. hydrodynamic lubrication
2. squeeze-film lubrication
3. Elastohydrodynamic lubrication –> main one during dynamic joint function
4. Weeping or self-lubrication
5. Boosted lubrication

Injury and healing

- superficial injuries (above tidemark) heal - deep injuries –> hematoma, fibrin clot/ inflammation –> fibrocartilage - infections –> hydrolysis of collagen and PGs, cells (–> release of lysosomal enzymes) - OA

1. collagen disruption
   1. → PGs can attract more water
      1. decreased Young's modulus –> decreased ability to bear load
   2. loss of lubricant –> increased interfacial wear
   3. fatigue wear and accumulation of microscopic damage
2. chondroitin/keratan sulphate ratio increases

Treatment

Non-operative

Physical therapy `````````````` - immobilization –> cartilage atrophy - Salter (1989): CPM –> FT defects in rabbits

Oral visco-supplementation `````````````````````` - Glucosamine

1. amino-monosaccharide sugar
2. naturally occuring component of the GAGs keratan sulphate andn hyaluronate
3. in-vitro inhibition of PG synthesis by IL-1 and suppressing the inflammatory response of neutrophils
4. some benefit in RCTs
5. 1500 mg/day

- Chondroitin

1. GAG

Intra-articular visco-supplmentation `````````````````````````````` - MW: Low (Hyalgan), intermediate (Orthovisc), HMW (Synvisc) - limited evidence - no good studies showing good results

Operative Treatment

Abrasion arthroplasty `````````````````` - turns cartilage defect into a 'deep injury' - fibrocartilage healing

Autograft/mosaicplasty ``````````````````` - full thickness osteochondral grafts from superomedial margin of femoral notch

1. most useful in medial compartment
2. less useful for patellar

- superceded by newer tissue engineering therapies

Allograft ```````` - mostly for malignant tumors - cartilage is immunoprivileged tissue - spore-forming organism infection

Periosteal/perichondrial mesenchymal stem cells

- cambium layer - type II collagen and high PGs seen in repair tissue - no convincing reports of efficacy

Chondrocytes from mesenchymal stem cells

- bMSC isolation –> 3D matrix –> defect

Autologous chondrocyte implantation (ACI)

- Brittberg (1994) - harvest –> ex vivo expansion –> collagen gel carrier - reinserted and periosteal flap sutured - newer MACI

Role of growth factors

- TGF, IGF-1, FGF –> chondrocyte proliferation - IGF-1 stimulate collagen and PG production - BMPs - limited success in human trials

Viva Questions

- What is the composition of articular cartilage? - Draw the structure of articular cartilage - How are the functions of articular cartilage? How is structure related to function? - What pathological processes are involved in the develop of osteoarthritis? - What are the different options available for treating cartilage defects?

Revisions 2013-02-12: Original notes transferred from Evernote