Podcast
Questions and Answers
Which of the following roles do matrix metalloproteinases (MMPs) NOT play in tissue dynamics?
Which of the following roles do matrix metalloproteinases (MMPs) NOT play in tissue dynamics?
In cancer biology, how does integrin expression change when compared to healthy tissue?
In cancer biology, how does integrin expression change when compared to healthy tissue?
What is the effect of ECM modification on cell behavior during wound healing?
What is the effect of ECM modification on cell behavior during wound healing?
What pathological condition is associated with extensive degradation of ECM due to elevated MMP activity?
What pathological condition is associated with extensive degradation of ECM due to elevated MMP activity?
Signup and view all the answers
How do changes in ECM stiffness relate to cancer progression?
How do changes in ECM stiffness relate to cancer progression?
Signup and view all the answers
Which statement accurately describes the role of extracellular matrix (ECM) in wound healing?
Which statement accurately describes the role of extracellular matrix (ECM) in wound healing?
Signup and view all the answers
What is the primary function of matrix metalloproteinases (MMPs) in the extracellular matrix?
What is the primary function of matrix metalloproteinases (MMPs) in the extracellular matrix?
Signup and view all the answers
In pathological conditions, how does the extracellular matrix typically change?
In pathological conditions, how does the extracellular matrix typically change?
Signup and view all the answers
What role do integrins play in the context of extracellular matrix interactions?
What role do integrins play in the context of extracellular matrix interactions?
Signup and view all the answers
How is the extracellular matrix implicated in cancer progression?
How is the extracellular matrix implicated in cancer progression?
Signup and view all the answers
Which glycosaminoglycan primarily assists in maintaining the hydrated state of the extracellular matrix?
Which glycosaminoglycan primarily assists in maintaining the hydrated state of the extracellular matrix?
Signup and view all the answers
What is a major consequence of mutations in laminin?
What is a major consequence of mutations in laminin?
Signup and view all the answers
Which factor is NOT typically associated with the function of proteoglycans in the extracellular matrix?
Which factor is NOT typically associated with the function of proteoglycans in the extracellular matrix?
Signup and view all the answers
What is the defining feature of elastic fibers in the ECM?
What is the defining feature of elastic fibers in the ECM?
Signup and view all the answers
Which type of collagen is primarily found in cartilage?
Which type of collagen is primarily found in cartilage?
Signup and view all the answers
Study Notes
Extracellular Matrix (ECM)
- The ECM is a non-cellular component found in all tissues and organs.
- It's a network of macromolecules that fill the extracellular space.
- It contains proteins, proteoglycans (carbohydrates), and minerals.
- Cells secrete the ECM.
- It forms a significant portion of connective tissues like cartilage.
- The composition and structure of the ECM vary between different tissues.
Learning Objectives
- Explore the general features of the dental/oral ECM.
- Identify and recognise the five key ECM components in oral tissues.
- Relate changes to the ECM caused by pathological processes.
- Understand the basic components of normal oral tissues.
Side Note
- Students should review the basic structure and function of proteins, carbohydrates, lipids, and nucleic acids.
- Review basic biochemistry.
- Basic sciences for Dental students should be consulted (likely a reading list).
What is the ECM?
- The ECM is the extracellular matrix.
- It's a non-cellular component found in all tissues and organs.
- This matrix is made up of macromolecules, including proteins, proteoglycans, and minerals.
- It's secreted by cells.
- The ECM in connective tissue makes up a significant proportion of the tissue.
- The ECM characteristics change based on the specific tissues such as cartilage.
Why is the ECM important?
- The ECM provides strength, support, and protection.
- It stores and presents growth factors.
- It acts as a scaffold for tissue repair.
- It's important for cell adhesion and migration.
- The ECM acts as a signal that affects cell function, including growth and survival.
- It establishes a tissue microenvironment.
Examples of ECM
- Basement membrane (basal lamina), found in epithelia, endothelia, muscle, fat, and nerves
- Elastic tissues, found in skin, lungs and large blood vessels
- Stromal or interstitial matrix, found in bone, teeth, cartilage, tendons, and ligaments
ECM in dental/oral complex
- The presentation describes a diagram showing the location of the ECM in the oral cavity, including different parts of the tooth anatomy (enamel, dentin, pulp, gum, cementum, periodontal ligament).
Extracellular Matrix Molecules
- Five main classes of macromolecules make up the ECM.
- Collagens: structural proteins in the ECM.
- Elastic fibers: examples include elastin and fibrillin
- Proteoglycans
- Glycosaminoglycans (GAGs): examples include hyaluronic acid, chondroitin sulphate, keratin sulphate, heparin sulphate.
- Adhesive glycoproteins: examples include laminin and fibronectin
Collagen
- Collagen is a main structural protein of the extracellular space.
- Types of collagen include type I (skin, tendons, bone), type II (cartilage, vitreous humor), type III (skin, muscle), type IV (basal lamina), and types V-XII (less abundant).
Elastic fibres
- Allow tissues to return to their original shape after stretching. e.g., artery, lung, skin, bladder
- Crosslinked arrays of tropoelastin
Proteoglycans
- Protein backbone with polysaccharide side chains.
- Large branching aggregates that retain water.
- Types of glycosaminoglycans (GAGs) include chondroitin sulfate (hyaline cartilage), heparin sulfate (basement membrane), keratin sulfate (cornea), and hyaluronic acid (skin).
Proteoglycans
- Proteoglycans can be small or large, like decorin or aggrecan.
- They bind to proteins and regulate their functions.
- Cell surface proteoglycans like syndecan act as co-receptors.
Glycosaminoglycans (GAGs)
- Major component of proteoglycans.
- Extremely long, negatively charged polysaccharides that resist compression.
- Form viscous, hydrated gels.
- Hyaluronan keeps cells apart.
- Facilitates cell migration and proliferation.
- Inhibits cell-cell adhesion.
Adhesive glycoproteins - Fibronectin
- Large dimer of nearly identical proteins.
- Soluble in plasma.
- Binds to other proteins.
- Arg-gly-asp (RGD) sequence mediates cellular binding via integrins.
Adhesive glycoproteins - Laminin
- Trimeric cross structure.
- Binds to cells and other proteins.
- Major component of basal lamina.
- Involved in cell differentiation, adhesion, and migration.
- Mutations can cause conditions like junctional epidermolysis bullosa and nephrotic syndrome.
Basement membrane (BM)
- Specialized ECM.
- Provides cell attachment.
- Separates cells (epithelium, connective tissue).
- Allows cell division.
- Supports filtration in the kidney.
Interactions with the ECM
- Cells interact with the ECM through membrane-bound receptors like integrins.
- Specific integrin pairings determine ligand binding.
- Mediates cellular effects.
- Bidirectional signalling molecules are involved.
ECM- mineral
- ECM can be mineralised.
- Examples include calcium hydroxyapatite in bone (65%), dentine (70%), and enamel (96%).
- Provides mechanical stiffness to the tissue.
Modifications of ECM
- Cells modify the ECM around them.
- Enzymes like matrix metalloproteinases (MMPs) break down the ECM.
- ECM breakdown can create pathways for cell migration.
- The ECM releases or activates growth factors.
- ECM changes occur during wound healing and in diseased states like cancer.
MMPs
- Old names of collagenases, gelatinases, and stromelysins are replaced by numerical designations.
- MMP-1 and MMP-9 are important enzymes.
- Matrix metalloproteinases (MMPs) are also membrane bound.
- MMPs regulate the amount of ECM degradation and remodelling impacting cell migration, wound healing and angiogenesis.
- MMPs can activate growth factors and produce other bioactive molecules.
ECM - mechanics
- ECM can have different stiffness and elasticity based on composition (collagen, elastin).
- This affects cell behaviour and gene expression.
- Integrins act as mechanosensors.
- Stiffness changes can be linked to diseases like fibrosis and cancer.
ECM in aging, wound healing and disease
- The ECM is impacted by aging, wound healing and diseased states.
ECM in wound healing
- The ECM plays a part in wound healing processes.
Cancer: the matrix is now in control
- The ECM is traditionally viewed as a facilitator for tumor progression.
- This new understanding highlights the ECM's role in initiating the oncogenic transformation of epithelial cells.
- The ECM is a complex molecular network that provides a scaffold for cell organization. However, this framework also serves as a reservoir for regulating cell function. Important processes like cell growth, differentiation, survival, and motility are often impacted by components of the ECM.
ECM & integrins in cancer
- ECM and integrin expression are altered in cancer.
- Normal cell-cell and cell-ECM interactions are disrupted in cancer.
- Integrin signaling influences cell growth, anoikis, and cell migration (invasion).
- Targeting the ECM and integrins might be valuable in anti-cancer treatments and imaging.
Fibronectin binding integrin expression (ανβ6) in oral cancer
- The specific interaction between fibronectin and the integrin avb6 is important in oral cancer.
Tumour metastasis
- Tumour metastasis involves:
- Decrease in cell-cell contact,
- Breakdown of the basement membrane (BM).
- Stromal invasion
- Endothelial BM breakdown.
- Attachment and invasion of the stroma
- Re-growth with angiogenesis
MMPs in disease
- Extensive ECM degradation occurs in disease.
- Includes periodontitis and rheumatoid arthritis.
- Tumour cell invasion and metastasis are also linked to MMP activity, like carcinoma breaking basement membranes and invading surrounding stroma.
- MMP inhibitors are studied for therapeutic use.
Summary
- The ECM is a complex mixture of extracellular proteins, proteoglycans, and minerals.
- Cell-matrix interactions regulate cellular behavior.
- The composition of the ECM varies depending on the location in the body.
- ECM modifications are important in healing and diseased states.
Summary (alternative perspective)
- Collagens are triple helical proteins with non-collagenous domains that have structural roles and important post-translational modifications.
- Fibronectin is an adhesive glycoprotein in the ECM and plasma.
- Proteoglycans consist of GAG chains attached to a core protein.
- Laminins are major components of basement membranes.
- Matrix metalloproteinases (MMPs) contribute to degradation and remodelling of the ECM.
- Integrins are heterodimeric proteins, which mediate cell adhesion to the extracellular matrix.
Mini Research Task
- Research task suggestions include:
- Dentinogenesis imperfecta
- Papillon-Lefèvre syndrome
- Scleroderma
- Ectodermal dysplasia
- Scurvy
- Ehler's-Danlos syndrome
- Marfan Syndrome
Further reading
- List of relevant websites/articles for further study on the ECM.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
This quiz focuses on the extracellular matrix (ECM) in dental and oral tissues, exploring its general features, key components, and the impact of pathological changes. Understand the significance of the ECM in connective tissues like cartilage and its varying structures across different tissues.
