BIOM30002 Lecture Notes - Lecture 8: Synovial Fluid, Hyaline Cartilage, Hyaluronic Acid
12 Jun 2018
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L8 Synovium in health and disease
Summary
Part 1: Synovium, inflammation and cytokines in RA
- Healthy synovium consisting of synovial fibroblasts and macrophages, is critical for joint
mobility and cartilage nutrition.
- RA is characterised by proliferation of synovial lining layer, associated with
neovascularisation (new vessel) and infiltration by inflammatory cells.
- Cytokines, chemokines and growth factors are released by cells present in the inflamed
synovial tissue which promote inflammation and joint destruction.
- T cells, B cells, macrophages, synovial fibroblasts are present within RA joint and contribute
to inflammation and joint destruction.
- TNF, IL-1, IL-6 and MIF are pro-inflammatory cytokines which are key mediators of
inflammation in RA.
- JAK-STAT signalling is also important contributor to synovial inflammation in RA
- TNF is a valid therapeutic target for the treatment of arthritis.
Part 2: Animal models of RA
- Different models have different mechanisms of arthritis initiation (eg. Immune-induced and
genetic models)
1. Collagen-induced arthritis (CIA): induced by immune reaction to foreign collagen,
dependent on T and B cells
2. hTNF.Tg mice: dependent on elevated expression TNF, independent of T and B cells
- TNF inhibition in both CIA and hTNF.Tg mice reduces synovial inflammation and reduces
bone erosion
- Important to keep in mind that the limitations of the animal models when designing
experiments and interpreting results
>eg. Arthritis is dependent on IL-1 expression
- Invaluable to the identification and validation of therapeutic targets for the treatment of RA
Content
Pathogenesis of RA - heterogeneous
- Environmental factors
1. Oral: periodontitis
2. Lung: smoking, pollutants
3. Gut: microbiome
- Epigenetic modification
1. Methylation of histone > heterochromatin > dense > hard to read and transcript
2. Acetylation of histone > euchromatin > loosen > easy to read and transcript
3. Phosphorylation of histone
- Susceptibility genes
These triggers alteration of post-transcriptional regulation and autoimmunity
- Loss of tolerance > autoimmune antibodies, ACPA & RF in secondary lymphoid tissue
Transition to arthritis (clinical)
- Synovitis
- Structural damage: erosion of bone and cartilage
- Coexisting condition (extra-articular manifestation)
Healthy synovium VS RA synovium
Healthy synovium
- Synovium: a thin membrane that extends from skeletal tissue at interface of cartilage and
bone and lines the capsule of diarthrodial joints
- To separate ECM and synovial site
Healthy synovium structure
1. Intima (synovial lining layer)
Interface b/w joint cavity and subintima
Contains cells called synoviocytes
2. Subintima (sublining layer)
Connective tissues that become denser closer to the joint capsule
Contains blood vessels, lymphatic vessels and nerves
Healthy synovium functions
- Facilitates movement
1. Highly deformable > freely mobile to allow movement
2. Non-adherent properties (do not stick bone and cartilage)
3. As lubricants to minimise “wear and tear”
Hyaluronan: viscous, effective shock absorption and prevent fluid loss
Lubricin: protects cartilage surfaces from protein deposition and cell
adhesion; inhibit synovial cell overgrowth
- Contributes to formation of synovial fluid
- Chondrocyte nutrition via solute diffusion from synovial fluid
Intima (inner lining)
- 2 distinct cell populations
1. Fibroblast-like synoviocytes (Type B synoviocytes) - 80%, CD55+
Produce lubricin and hyaluronan (lubrication)
Produce collagen and fibronectin > for ECM (cell adherence) and formation
of subintima
Mesenchymal origin
2. Macrophage-like synoviocytes (Type A synoviocytes) – 20%, CD68+
Primarily phagocytic > for clearance of debris in joint
Express receptors for Fc domains of IgG > for recognition of immune
complex
Derived from blood mononuclear cells
Present antigen (macrophage-like)
Inflamed synovium in RA
- Contains:
1. Osteoclast
2. Fibroblast
3. Macrophage
4. Dendritic cell
5. T cell
6. Plasma cell
7. B cell
8. Mast cell
9. Neutrophils (less common)
- Early onset, causing:
1. Inflammation
2. Erosion of bone and cartilage
3. Hyperplastic synovial lining (intima)
4. Infiltration of inflammatory cells into subtima
5. Extensive angiogenesis – neovascularisation/neoangiogenesis
6. Ectopic lymphoid neogenesis > localise immune centre
7. Deposition of fibrin in active disease > have inflammatory properties
Pannus
- Pannus = inflamed synovial tissue “creeps” over the cartilage and bone tissue of the joint
1. Rich in fibroblast-like cells
2. Contains macrophages
3. Contains fewer immune cells than the peripheral inflamed synovial tissue
4. Hypoxic micro-environment
- Cells within the pannus release factors > destroys articular cartilage and bone
Document Summary
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