L23 - Synovium Flashcards
What is synovium and where it is located?
Thin membraneous structure that extends from skeletal tissue at interface of cartilage and bone and lines the capsule of diarthodial (synovial) joint. It is made of two layers: the intima and the subintima
What is the difference between the intima and subintima?
- The intima is the synovial lining layer which is 1-3 cells deep. These cells are called synoviocytes (of which there are two cell populations).
- The subintima is connective tissue that becomes deeper the closer it gets to the joint capsule. It contains blood vessels, lympathic vessels and nerves
What is the order of the layers of the joint from the outer layer to inner layer?
Capsule, Subintima, Intima, Synovial Fluid
What are the 3 forms of synovial tissues and their appearance?
•areolar form
- predominant in large joints and a very prolific synovial lining layer that is several layers deep.
- loose connective tissue (subintima) which is underlying that lining layer (intima).
- Less collagen produced in this tissue
large amounts of vascularisation.
•fibrous tissue layer
- greater number of collagen fibrils
- distinct cell lining layer which is 1-2 cells thick
- generally more closer to the skeletal tissues.
•fatty
- With age, there is a greater deposition of fatty tissue which contains plenty of adipocytes.
- Only a very thin lining layer, not too much connective tissue within the synovial tissue.
List the functions of synovium:
- facilitate movement between non-deformable strutures in joint
- provision of lubricants to minimize wear and tear of joint (hyaluran & lucricin)
- formation of synovial fluid
- cartilage nutrients
Roles of TNF in RA
- Proinflammatory cytokine release (IL1, IL6, IL23 etc)
- Prostaglandin 2 production (inflammatory mediator)
- Chondrocyte activation -> metalloproteinase - Osteoclast activation -> bone resorption
production, cartilage destruction - Cytokine release -> leukocyte accumulation
- Hepcidin induction in liver as part of acute-phase response
- Leukocyte accumulation -> induction/maintainece of HLA class II expression
- Endothelial cell activation -> upregulation of E-selectin and VCAM-1; leukocyte accumulation
- Angiogeness
(PP COCHLEA)
What are the roles of IL1 in RA?
- Activates leukocytes, endothelial cells, and synovial fibroblasts
- Induces expression of chemokines, cytokines
- Induce metalloproteinase production by chondrocytes and synovial fibroblasts -> cartilage destruction
- Induce expression of factors required for osteoclast differentiation -> bone resorption
How are collagen-induced arthritis (CIAs) rats made?
1) Immune CIA with foreign Collagen Type II/Freund Complete Adjuvaent at base of tail by intradermal injection
2) APCs take up antigen and migrate to lymph node to to present to T cells and activate B cells
3) Day 21, booster injection given with collagen type II. Results in local synovitis, infiltration of synovium with inflammatory cells (hallmark of RA)
4) Staining for TRAP maks osteoclasts -> bone destruction
What are the pros and cons of CIAs?
Pros:
-symmetrical arthritis affecting knees and paws: synovial inflammation, significant bone and cartilage erosion
-dependent on T and B cells, expression of certain MHC II alleles (similar to humans in which genetics affect severity of RA)
-TNF and IL1-B expression is elevated so that inhibition of either of these cytokines reduces arthritis onset and severity
- RF reported to be produced
Cons:
-Disease susceptibility is dependent on exprssion of certain classes of major MHC calss II molecules -> only certain mouse strains are susceptible (DBA/1 moice most susceptible. although protocols now available to induce CIA in some mice. This is less robst and fewer mice develop disease
-Antibodies to collagen is produced so to an extent, this is an artifical system
What are the features of the hTNF.Tg mouse?
- Genetically engineered to over-express TNF
- Develop arthritis spontaneously, affecting knees and paws
- Synovial hyperplasia, inflammatory cell infiltrates from 3-4 weeks of age
- Full blown arthritis by 20wks
- Inflammation, pannus formation, cartilage destruction, focal bone erosions and systemic bone loss
- Chronic form of RA like in humans
Blocking TNF will reduce or block disease severity
Dependent on IL1/IL1R expression and signalling
What are the pros and cons of the hTNF.Tg mice?
PRos:
- Reliable, robust arthritis which is chronic
Useful to assess effect of TNF inhibition in treatment of arthritis
Cons:
- Even though IL1 is essential to RA, this is a TNF model -> role of other cytokines may not be as important
-RA s not dependent on T or B cells as a mouse which lacks the ability to activate T or B cells can still develop RA.
