Skeletal 1

• Andreas Vesalius


  • Wrote De humani corporis fabrica libri septem (1543)
• Functions of the skeletal system

  • Protection
  • Support
  • Attachment points for ligaments and muscles
  • Houses hematopoietic tissues (marrow)
  • Storage reservoir for calcium and phosphorus (Helps to regulate blood calcium levels, necessary for proper nervous system function)
• William Cheselden

  • Wrote Osteographia (1733)
• Bone

  Mineralized connective tissue
• Myosepta in a teleost fish

  • Note the alignment of the neural/hemal spines and ribs with the sheets of connective tissue between sequential segments of muscle blocks (myomeres)
• Scleral Cartilages

  • Support the sclerae of the eyes
  • Can be permanent
  • Sometimes replaced/transformed into bone (sclerotics)
• Sclerotic bones

  • In a leaf-tailed gecko, Uroplatus phantasticus
  • In a chicken embryo, Gallus gallus
  • In an ichthyosaur

  
• Pathological ossifications

  • Ossification of fibrous tissues, such as ligaments, muscles and tendons
  • Can be the result of trauma, or rare hereditary conditions
  • Ankylosing spondylitis (also called "bamboo spine")
  • Fibrodysplasia ossificans progressiva (also: myositis ossificans progressive or 'Stone Man Disease')
• Embryonic tissue origin from the Mesoderm & Neural Crest
• Special skeletal structures (face, teeth, visceral arches) are derived from several sources, the rest is effectively connective tissue (mesoderm) that is variably remodeled into bone

  
• Living bone includes three principal structural components


  • Fibrous collagen component
  • Mineralized framework
  • Vascular/cellular material

  
• Midshaft section of a human longbone with all soft tissue removed

  • The mineralized framework is all that remains

  
• During bone formation, an extracellular matrix (ECM) is laid down as a scaffold, over which the bone organ will be built
• The ECM is principally the protein Type 1 collagen
• Collagen comprises ~ 33% of the dry weight of bone
• Virtually all the remaining dry weight is the mineral framework
• Osteoblasts deposit calcium phosphate, in the form of hydroxyapatite, within the ECM scaffold
• An extensive network of blood vessels exists within the bone
• Bones are living/dynamic tissues, not inert masses within the body
• Collagen

  • A family of proteins with many different types based on their primary, secondary, or tertiary structures
  • They form the main protein component of connective tissues
  • ~25-30% of whole-body protein count in mammals
  • Type 1: found in tooth, bone, connective tissues, scar tissue, blood vessels
  • Type 2: found in Hyaline cartilage
  • Type 3: found in elastic tissues
• Basic collagen unit

  • An alpha-chain consisting of a sequence of amino acids
  • 3 alpha chains are twisted into a triple helix 'collagen molecule'
  • Multiple collagen molecules are bundled into 'fibrils'
  • Many fibrils are woven into collagen 'fibers'
• Collagen Alpha structure

  • 3 α-chains comprise a single triple helix molecule
  • Glycine (Gly) is found at almost every third residue (~33% of amino acid residues)
  • This comprises the classic "Collagen Triad": X – Y – Gly
  • Glycine is four-fold degenerate, encoded by GG-n codons
• Collagen Alpha structure

  • Proline (Pro) is another extremely important amino acid in collagen formation; usually makes up about 17% of residues
  • Proline is four-fold degenerate, encoded by CC-n codons
• Collagen Alpha structure

  • Hydroxyproline (Hyp) and Hydroxylysine (Hyl) are derived from Proline (Pro) and Lysine (Lys), respectively
  • Lysine is coded by AAA or AAG
• Hydroxyproline is a major component of vertebrate collagen (~10% of AA residues)
• In the collagen triad X-Y-Gly, Hydroxyproline at the Y position (X-Hyp-Gly) increases the stability of the triple helix, permitting tight twisting into fibril structures
• The enzymatic cofactor that serves as a catalyst for the conversion of Pro and Lys into Hyp and Hyl is Vitamin C
• Vitamin C is necessary for the formation of collagen
• Deficiency in Vitamin C causes the condition known as scurvy
• Defective collagen (esp. Type 1) doesn't form proper triple helices, preventing the formation of strong connective tissues
• Gums deteriorate and bleed, with loss of teeth; skin discolors, and wounds do not heal
• Proline


  Amino acid
• Hydroxyproline

  Amino acid derived from Proline
• Hydroxylysine

  Amino acid derived from Lysine
• Lysine

  Amino acid
• Collagen


  Protein with alpha structure
• Hydroxyproline (Hyp) and Hydroxylysine (Hyl) are derived from Proline (Pro) and Lysine (Lys), respectively
• Proline


  Four-fold degenerate, encoded by CC-n codons
• Lysine


  Coded by AAA or AAG
• The specific triad, Prol-Hyp-Gly, is especially common in Type 1 collagen, found in bone and connective tissues