Cartilage regeneration and repair Flashcards
How is the turnover of cartilage?
Cartilage has limited intrinsic regeneration capacity
Low turnover of tissue
Fetal cartilage can regenerate completely
TRUE or FALSE
TRUE
Remodeling capacity of cartilage tissue
Cartilage is prone to several insults related to increased joint mechanical loading
Chondroctes can in a limimted manner repair cartilage defects
Matrix however shows poor lateral integration
What are features of osteoarthritis?
Chronic degeneration of cartilage tissue matrix
Leads to a loss of joint function
What happens to the severity of OA if subchondral bone is involved?
Condition is exacerbated
Cells invading from subchondral bone synthesize collagen type I ECM
What causes the changes in cartilage in OA?
Chondrocytes alter their gene expresssion profile
Make a catabolic phenotype
Synthesize increased levels of proteolytic enzymes that degrade cartilage ECM
Degradation of these componenets leads to weakening of the cartilage ECM
Causes roughening of the cartilage tissue and deep fibrillation of the matrix
What are examples of enzymes released by chondrocytes that damage cartilage?
Collagenases - degrade collagen (MMP-13)
Aggrecanases - degrade aggrecan (ADAMTS5)
What happens to the chondrocytes in OA?
Proliferate by a process of clonar expansion and die
What increases the chances of developing OA?
Obesity
Age
Gender
Inflammation
Genes and epigenetics
Over-use of joints
What happens to the bones of OA patients?
Thickening of the subchondral bone following reactive remodelling
Leads to the formation of osteophytes, bone cysts and epiphyseal expansion
Why do bones change during OA?
Represent mechano-adaptation of the bone to the altered mechanical environment
Can changes to the bone during OA be observed?
Yes
These changes are diagnostic on plain radiographs
What are osteophytes?
Form by a process of endochondral ossification
What is a key early event in the pathogenesis of OA?
Degradation of aggrecan by aggrecanase
Aggrecan protects collagen from proteolytic degradation
Is aggrecan degradation reversible?
Yes
Is collagen degradation reversible?
No
What are MMPs?
Matrix metalloproteinases
Calcium-dependent
Degrade collagen molecules and other ECM proteins
Calcium-dependent zinc-containing endopeptidases
Synthesized as inactive zymogens with pro-peptide domain
What does ADAMTS stand for?
A disintegrin and metalloproteinase with thrombospondin motifs
Deletion of catalytic domain of ADAMTS5 in transgenic animal confers resistance to cartilage destruction
TRUE or FALSE
TRUE
What type of condition is Achondroplasia?
Autosomal dominant mutation
Characterised by shortened limbs
What causes Achondroplasia?
Caused by constantly active FGF receptor 3
Causes inhibition of chondrocyte proliferation and differentiation
Reduced size of cartilage anlagen
Impairs endochondral ossification
Reduced bone growth as growth plate function is impaired
Does Achondroplasia affect all the bones?
NO
Only the ones formed through endochondral ossification
Not the ones formed through intramembranous ossification
What is rheumatoid arthritis?
Severely debilitating, painful degenerative joint disease
Autoimmune disease
Progressive destruction of the joints by immune cells
What is the presentation of RA?
Chronic inflammation of the joints
Deformation and loss of motility/ joint function
What are the treatments for RA?
No curative treatments available
Therapy using anti-inflammatory drugs
Novel biologics to block immune response
What is essential to improve outcome of RA?
Early diagnosis
Tailored therapy
Describe a clinical trial targeted at RA
Intraarticular interleukin-1 receptor antagonist gene therapy
Describe the process of Matrix-assisted chondrocyte implantation
Adult chondrocyte isolated from non-load bearing part of hyaline cartilage
Patient-specific chondrocytes are expanded in in vitro culture
Cells are re-implanted into defect
Covered in synthetic membrane (allogenic collagen membrane or periost)
How do you obtain the chondrocytes from the non-load bearing parts of the hyaline cartilage?
Extract material
Tissue is digested
What are the problems with MACI?
Conservation of chondrogenic phenotype during 2D expansion
Cost
Donor site morbidity
What were the results of MACI?
Good results in younger patients
Not always reproducible
