MMP's and the Role of Zinc in Wound Healing
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Matrix metalloproteinase (MMP) and Zinc play an important role in wound healing. As MMP's are dependent upon Zinc, you can't have one without the other. Without MMP's you can not have collenganese activity (or other endogenous proteolytic enzymes) resulting in a wound that will not heal. For more information on this topic and many others regarding wound healing, check out our other presentations here.
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Abstract
1) Protein phosphatase 5 (PP5) regulates the differentiation of mesenchymal stem cells into either adipocytes or osteoblasts through phosphorylation of PPARγ and RUNX2. 2) Mice deficient in PP5 have increased bone formation and decreased fat accumulation in bone marrow. 3) Experiments analyzing mice with tissue-specific knockout of PP5 in adipose tissue or long bones found that loss of PP5 in adipose tissue increased trabecular bone, while loss in long bones increased cortical bone thickness, implicating PP5 in regulating the balance between bone and fat formation in different tissues.
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1) Protein phosphatase 5 (PP5) regulates the differentiation of mesenchymal stem cells into either adipocytes or osteoblasts through phosphorylation of PPARγ and RUNX2.
2) Mice deficient in PP5 showed increased bone formation and decreased marrow adipocytes, suggesting PP5 promotes adipogenesis over osteogenesis.
3) Experiments on mice with tissue-specific PP5 knockout found loss of PP5 in bone led to increased cortical bone thickness while loss in adipose tissue led to increased trabecular bone formation, demonstrating PP5 regulates the balance between bone and fat formation in different tissues.
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Wound healing involves three phases: inflammatory, proliferative, and maturational. Primary healing occurs when wound edges are in direct contact while secondary healing involves granulation tissue formation. Many factors can affect wound healing including infection, nutrition, steroids, ischemia, and diabetes. Growth factors are important for different stages of healing. Stem cells can help regenerate damaged tissue. Aberrations like keloids and hypertrophic scarring exist. New treatments include skin substitutes, dressings, growth factors, and therapies like hyperbaric oxygen and offloading casts.
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- 1. MMP’s and the Role of Zinc inWound Healing Dr. MitchellV. Kaminski, Jr. Board Certified in Nutrition, Surgery andWound Healing
- 2. Origin of Zinc – Crab Nebula supernova Zinc complete electron shell therefore powerful antioxidant Used by permission ofThe University ofTexas McDonald Observatory. Green – Hydrogen (H) Red – Nitrogen (N) Reddish - Sulfur (S) Blue – Oxygen (O) Violet – Helium (He) Brown – Polycyclic aromatic Hydrocarbons (C+) CHO = Carbohydrate & Fat CHON = Protein
- 3. Role of Zinc • Total Body Content 1500-3000mg • (IronTBC – 2300-3800mg) • 300+ Enzyme Reactions • Epidermal integrity & resistance • Antioxidant • Sex hormone, insulin & serotonin • EU Zincage Study • Chromosomal RNA/DNA transcription • Genome stability • Signal triggering • MMPs • Immunity – neutrophils, killer cells, macrophages
- 4. Determining a Zinc Deficiency •Serum zinc vs. functional test
- 5. ZincTasteTest (ZTT) •Zicam oral spray •Repulsive taste to healthy adult •Gustin
- 7. Zinc Deficiency •Genetic or acquired Acrodermatitis Enteropathica (Genetic) Acquired
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- 10. Biofilm •Complex community of microorganisms •Characterized by high cell density •Extracellular polymer matrix •Physical barrier against antimicrobial •Facilitates adhesion (tissue & foreign bodies) •Exopolysaccharide
- 11. Necrotic Debris and Biofilm •MMP9 •Tenacious •Mechanical Removal
- 12. MMPs •MMPs manufactured by macrophlages and membrane bound •15 of 20 MMPs found in wounds – collenganese activity •MMP9 = DirtyWound •MMPs digest all proteins in ECS & basement membrane
- 13. Extracellular matrix • Basement membrane • Proteoglycans • Heparan sulfate • Chondroitin sulfate • Keratan sulfate • Non-proteoglycan polysaccharide • Hyaluronic acid • Fibers • Collagen • Elastin • Other • Fibronectin • Laminin
- 14. MMP Inhibitors •4 tissue families •TIMP-1,TIMP-2,TIMP-3,TIMP-4 •Common cysteine switch
- 15. Conclusion • Critical to wound healing • MMPs are zinc dependent • Serum level unreliable • Functional test – simple & reliable • Proposal: Recommended lower limits must be reevaluated • Current: 70 ug/dL • Proposed new level be consistent with recovery of normal ZTT