Bones, Ligaments & Tendons PDF

Bone Learning Outcomes By the end of this lecture students should be able to: Identify the gross anatomical and morphological features of (long) bone Describe the cellular and molecular constituents of bone and their involvement in thickening, growth and remodelling Identify and describe...

Bone Learning Outcomes By the end of this lecture students should be able to: Identify the gross anatomical and morphological features of (long) bone Describe the cellular and molecular constituents of bone and their involvement in thickening, growth and remodelling Identify and describe the main features of a Haversian system Explain how bones are involved in calcium homeostasis BIOS3100: Musculoskeletal Physiology Dr John Harris (Oct ’24)  Tissue Types Connective tissue includes bones, ligaments, tendons Comprised of specialised cells within extracellular material of specific molecules they produce Connect, support and anchor body parts i.e. tendons – skeletal muscle to bones; ligaments – bones to bones  Connective Tissue Structure Three main components: ‒ Cells ‒ Fibrous elements (e.g. collagen fibres) ‒ Ground substance – special proteins Cells are not compacted and are separated by abundant extracellular matrix (ECM) Variation in composition/structure of ECM (which may be a fluid, solid or gel) gives connective tissue its morphological and functional characteristics  Connective Tissue Cells Various cell types are embedded within all connective tissues Named by the tissue they produce and maintain: ‒ Bone = osteo- (cytes, blasts, clasts) ‒ Cartilage = chondro- ‒ Muscle = myo- ‒ Tendons = teno-  Extracellular Matrix (ECM) Structure ECM consists of: Fibrous elements ‒ Collagen – strong, flexible but inelastic (several types, type I most common) ‒ Reticular fibres – fine collagen type III fibres, networks of these fill space between tissue and organs ‒ Elastin – elastic properties – percent varies according to tissue function Ground substance (non-fibrous protein and other molecules) ‒ Amorphous gel-like substance surrounds cells ‒ Components include: hyaluronic acid, proteoglycan Water  Skeletal Systems A skeletal system forms the framework of the body Vertebrates have endoskeletons Invertebrates have exoskeletons or hydrostatic skeletons  The Purpose of a Skeleton Structural to support the body Protection of soft tissues and internal organs against traumatic injury Locomotion by providing rigid rods and levers by which muscles can act to effect movement hence interaction with external environment Calcium homeostasis – bone acts as a reservoir to regulate free calcium (and phosphorus) in ECF (plasma) within very narrow limits [Manufacture of blood cells in haematopoietic red bone marrow]  Bone Tissue Cells ‒ Osteocytes ‒ Osteoblasts ‒ Osteoclasts Extracellular matrix ‒ Organic (osteoid) ‒ Inorganic (minerals) Vascular spaces  Bone: Cell Types The cell types in bone are: Osteoblasts (create) ‒ Responsible for bone formation e.g. growth ‒ Line bone surfaces ‒ Produce osteoid and mediate its mineralization Osteocytes ‒ Mostly inactive osteoblasts trapped within formed bone ‒ Maintain general structure of bone ‒ Assist in nutrition of bone Osteoclasts (break) ‒ Resorb bone via phagocytosis ‒ Important for bone remodelling  Osteoid The ECM of bone is comprised of osteoid, an organic mucopolysaccharide-rich semi-solid gel (ground substance) containing cable-like collagen fibres Produced by osteoblasts Secreted onto existing bone surface Provides tensile strength  Components of Osteoid Collagen type I ~90% (trace type V) ‒ Strong, inert fibrils ‒ Important structural component Embedded in a ground substance of water and Glycoproteins ‒ Osteonectin, osteocalcin ‒ Bind collagen & mineral Proteoglycans ‒ Biglycan, decorin ‒ Bind growth factors Bone sialoproteins ‒ Osteopontin, thrombospondin ‒ Associated with cell adhesion  Bone Matrix (Inorganic Minerals) Incorporation of calcium phosphate in the form of inorganic hydroxyapatite (Ca10(PO4)6(OH)2) Normally in solution in ECF but in bone crystalizes around collagen fibres to ossify and harden bone Minerals comprise 60-70% dry weight Makes bone radio-opaque Radiograph of a horse "fetlock" joint Provides compressional strength whilst still being relatively lightweight  Woven and Lamellar Bone Two main forms of bone depending on how collagen fibres are organised: woven and lamellar bone Woven bone ‒ Random arrangement of collagen in the osteoid ‒ “Quick and dirty” formation by osteoblasts o Young growing animal o Fracture repair Lamellar bone ‒ Regular parallel bands of collagen in thin osteoid sheets ‒ Physically stronger, resilient  Gross Structure of a Long Bone Diaphysis – fairly uniform cylindrical shaft Epiphysis – flared articulating knob at either end of diaphysis Bone marrow fills central cavity of bone (blood cell production) Periosteum – connective tissue sheath covering outside of bone  Gross Bone Morphology Two types of bone tissue ‒ Compact (Lamellar) – dense outer part of bone (also referred to as the cortex) ‒ Spongy (Trabecular) – “lacy” inner core (also referred to as medullary or cancellous) Epiphyseal plate – cartilage layer at each end of growing bone between epiphysis and diaphysis  Growth Periods Most mammals have two periods of rapid growth  Postnatal growth spurt in early life ‒ Increased body protein, mainly skeletal muscle  Pubertal growth spurt ‒ Increase in the magnitude and frequency of growth hormone (GH) release ‒ Increase in size (hypertrophy) and number of cells (hyperplasia) in soft tissue ‒ Promotes thickening and lengthening of long bones  Growth in Length (Ossification) Proliferation of chondrocytes (cartilage cells) in outer edge of epiphyseal plates next to epiphysis As new chondrocytes added on outer epiphyseal border, old chondrocytes on diphyseal border enlarge  Growth in Length (Ossification) 2 Leads to temporary widening of epiphyseal plate i.e. epiphysis moves further from diaphysis Matrix around enlarged old chondrocytes becomes calcified and die due to lack of oxygen and nutrients  Growth in Length (Ossification) 3 Osteoclasts remove dead chondrocytes/calcified matrix Osteoblasts from diaphysis invade space and produce new bone and capillary blood supply Epiphyseal plate (new chondrocytes) at original thickness  Involvement of Growth Hormone (GH) GH stimulates insulin-like growth factor (IGF-I) in the liver (hormonal release into circulation) and most tissues, including bone (local paracrine action) Bind to tyrosine kinase coupled receptors GH stimulates proliferation of chondrocytes in the epiphyseal plate and stimulates osteoblast activity as long as plate remains cartilaginous (“open”) Androgens (e.g. testosterone) also promote protein synthesis and bone growth but ultimately act to stop growth at the end of adolescence (i.e. complete ossification of epiphyseal plate = “closed”)  Growth in Thickness New bone added by osteoblasts (in periosteum) to outer surface of existing bone Osteoclasts concurrently remove bony tissue on inside adjacent to bone marrow cavity Hence as bone circumference increases, marrow cavity increases proportionally  Bone Remodelling Constituents of bone undergoing constant turnover due to concurrent bone deposition and resorption (remodelling) ‒ Keeps mechanical effectiveness of skeleton ‒ Maintenance of plasma Ca2+ levels Osteoclasts attach to osteoid (ECM) and form “ruffled” membrane – increases area in contact with bone Osteoclasts secrete organic acids (e.g. HCl) to dissolve hydroxyapatite and enzymes to breakdown ECM creating a cavity Bone Remodelling 2 Osteoblasts migrate into cavity and fill with osteoid which mineralises to form new bone Formation/resorption rates about equal so total bone mass fairly constant in adult Facilitates: ‒ change in bone shape ‒ change in bone material ‒ repair of damaged bone ‒ release of mineral ions RANK Ligand and Osteoprotegerin RANK ligand increases the action of osteoclasts via activation of nuclear factor kappa-B (nF-kB) a transcription factor In contrast osteoprotegerin (OPG) suppresses osteoclast activity Balance between RANKL and OPG is important in determining bone density  Haversian System (Osteons) Compact bone comprised of units known as osteons Concentric layers of “entombed” osteocytes (lamellae) with a central canal containing blood vessels Osteoblasts on outer and inner surface (lining central canal) Osteoclasts located on surfaces where absorption occurring Osteons run parallel to long axis of bone  Osteocytic-Osteoblastic Bone Membrane Network of fluid-filled canals (canaliculi) allows exchange of substances between osteocytes/circulation Cytoplasmic extensions of osteoblasts and osteocytes connect at gap junctions – communication and material exchange Cell network separates mineralized bone from blood vessels  Maintenance of Plasma Ca2+ Levels Between osteocytic-osteoblastic bone membrane (OOBM) and mineralized bone in the canaliculi and surface of central canal is bone fluid Bone fluid contains small pool of readily available Ca2+; moved to plasma via Ca2+ pumps in OOBM stimulated by parathyroid hormone (PTH) - FAST Much larger stable pool of Ca2+ in mineralized bone; dissolution of bone stimulated by PTH (calcium and phosphate liberated) - SLOW  Some Further Reading Sherwood, L., Klandorf, H. & Yancey, P.H. (2013) Animal Physiology: From Genes to Organisms, 2nd Edition, Brooks-Cole/Cengage Learning, Pg 291-295, 323-328 Young, B., O’Dowd, G. & Woodford, P. (2014) Wheater’s Functional Histology: A Text and Colour Atlas, 6th Edition, Elsevier/Churchill-Livingstone, Chapter 10 Skeletal Tissues Tortora, G.J. & Derrickson, B.H. (2009) Principles of Anatomy and Physiology, 12th Edition, Wiley, Chapter 6 The Skeletal System: Bone Tissue