Ch 38 Tissues of MSK Flashcards
Define connective tissue
Hypocellular tissues containing tissue-specific mesenchymal cells within a specialised extracellular matrix
What is the most abundant protein in the body?
Collagen
What composes amorphous ground substance?
Nonfibrillar proteins, glycoproteins, proteoglycans, and proteolipids
What embryonic later do most of the MSK tissues arise from? What is the exception and what does it arise from?
Embryonic mesoderm
Exception = nucleus pulpous which arises from neuroectoderm
What is the correct name for MSK stem cells? List the 4 types of differentiation these cell may undergo
Multipotent progenitor cells
Osteogenic
Chondrogenic
Neurogenic
Adipogenic
What is process by which cells mount specific biologic responses to mechanical stimuli
Mechanotransduction
underlies many aspects of growth and adaptation of musculoskeletal tissues
Mechanical loading of musculoskeletal structures produces distributions of stress (force per unit area) and strain (deformation in a given direction) within tissue
What are the 2 types of response MSK tissues can have to stress/strain? Give an example of each
Physiologic response - eg fracture healing
Pathologic response - eg thickening and fibrosis of joint capsule in response to chronic instability
What form of MSK tissue does not show cellular interconnectedness?
Cartilage
tissues such as tendon/ ligament in which healing occurs through fibrosis, regional connectivity among scar fibroblasts is not effectively reestablished
This is likely to underlie the inferior mechanical properties
What structure do all collagens share?
Triple helices with disulphide bonds
List 4 types of collagen
fibril-forming collagens
(types I, II, III,V)
networking collagens (types IV, VI, VIII, and X)
Fibril associated with interrupted triple helices
Transmembrane
List the stages of tendon unit synthesis
tropocollagen -> collagen molecule –> fibril –> fiber –> fascicle –> tendon
What allows for a wide variety of fibrillar configurations that are specifically adapted to its functional requirements?
The hierarchical structuring
List three major components of the extracellular matrix
Collagen
Proteoglycans
Elastin
What is the basic structure of proteoglycans?
A core protein with glycosaminoglycan side chains
What are the 2 main types of proteoglycans?
Large aggregating proteoglycans - Have a back bone of hyaluronic acid giving it a high affinity for water leading to high hydration and turgiditiy - important for articular cartilage
Small leucine-rich proteoglycans - Roles in regulation of collagen fibrillogenesis and elastogenesis and modulation of growth factor signalling
What are responsible for the break down of proteoglycans?
Matrix metalloproteinases and aggrecanase
What is the most abundant GAG in the body?
Chondroitin sulphate
What GAG is prevalent in bone and cartilage?
Keratan sulphate
What extracellular matrix component is important as it provides a scaffold for other components to be laid down?
Fibronectin - also important for cell adhesion
How much elastic deformation can elastin fibres undergo? What is the maximum extension prior to loss of strength?
Can undergo elastic deformation of 70% of their resting length with a maximum extension of 220% before loss of strength
What cells make up the basic multicellular unit of bone?
Osteoblasts, osteocytes and osteoclasts
Where do osteocytes reside?
Encases within the bone matrix within individual lacunae
What cells are the major orchestrators of osteoclastic recruitment? Through which mediators?
Osteoblasts
M-CSF (monocyte colony stimulating factor)
RANKL
What percentage of water and mineral does bone contain?
5-10% water, 70% mineral.
What percentage of the extracellular matrix is composed of collagen?
90%
mostly type I with some type III and IV
What is the primary bone mineral?
Calcium hydroxyl-apatite
What forms the basic scaffold of bone?
Collagen fibrils
Configuration of which can give rise to different forms of bone
Lamellar bone - alternating orientation of highly organised layered pattern.
Woven bone - more loose and disorganised (formed in indirect fracture healing)
What law describes the continuous adaptive remodeling of bone?
Wolff’s Law (described by Julius Wolff 1892)
primary mechanotransducer in bone
osteocyte
osteogenesis, terminal differentiation of osteoblasts into osteocytes
Sclerostin
paracrine regulator of osteogenesis that is expressed exclusively in osteocytes in response to mechanical strain
Loss of osteocytes leads to decreased production of sclerostin, which in turn triggers proliferation and biosynthetic upregulation of osteoblasts
numerous inflammatory cytokines potentiate osteoblast-mediated recruitment and differentiation
Osteoclasts are thus recruited to a target area and resorb bone locally, creating a resorption pit, or Howship’s lacuna.
TGF-β family, insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), and matrix fragments that further stimulate osteoblast activity
resorption cycle
Osteoclasts undergo apoptosis and the resorption pit prepares for new osteoid deposition.
osteoblasts > surface of the pit, osteoid is deposited
osteoblasts become encased in new bone > turn into osteocytes,
re-estabilishing the downregulatory effect on nearby osteoblasts, ending the remodeling cycle
What is the water content of hyaline (articular) cartilage?
70% water
On a dry matter basis, what does articular cartilage consist of? (4)
50% collagen
35% proteoglycans
10% other glycoproteins.
Chondrocytes approx 2-10%
Describe the different zones of articular cartilage
Zones 1-3 are un mineralised, Zone 4 is mineralised and these are seperated by the tidemark (TM)
Zone 1 - “Superficia zone” - Highest cell density. Small flat chondrocytes orientated with their long axis parallel to the joint surface. This zone undergoes tension parallel to the surface
Zone 2 - “Transitional Zone” Larger and rounder cell profiles. Shear and compressive forces. Fibrils are consiting of perpendicular branches with branching smaller fibrils
Zone 3 - “ Radiate Zone” - Cells are larger and arranged with long axis perpendicular to joint surface. Compressive state predominates. Fibrils are larger, perpendicular and form a mesh-like structure
Thus, superficial layer forms a pre-stressed, wear-resistant diaphragm to withstand tension in the plane of the articular surface. The middle and deep zones are organised with the increasing ability to withstand compressive loads. The amount of proteoglycan increased with increasing depth.
How fast is cartilage and proteoglycan turnover in the adult dog?
Very slow!
Cartilage - 120yr
Protepglycans - approx 300d
What are the major forms of collagen and proteoglycan in articular cartilage?
Type II collagen - Forms a web-like structure providing tensile stiffness and strength
Aggrecan is the major proteoglycan - Rich in chondroitin sulfate and keratan sulfate side chains
Describe the two lubricants within an articular joint
Lubricin - a boundary lubricant. Most critcal under high load, low-motion conditions in which cartilage is most susceptible to wear and degradation.
Hyaluron - A viscous lubricant
What component of articular cartilage allows it to withstand tensile and compressive forces?
Tensile forces - Collagen fibrils
Compression - Proteoglycans.
Articular cartilages low permeability and high interal swelling pressure allow it to maintain hydration under pressure.
GAGs account for up to 75% of the osmotic pressure of proteoglycans and this contributes up to 50% of the compressive stiffness
Define fibrocartilage and give examples of fibrocartilage rich regions of the body.
Fibrocartilage is a specialised form of cartilage consisting of chondrocytic cells suspended in a dence extracellular matrix which is rich in type I collagen with relatively small quantities of proteoglycans.
Fibrocartilage is present within the annulus fibrosis, menisci, TMJ and parapatellar fibrocartilaginous insertions.
It also develops during degeneration or healing of many musculoskeletal tissues including bone, tendon, ligament and full thickness articular cartilage defects
List three types of tendons and give an example of each
some tendons surrounded by synovial sheath > low-friction
Aponeuroses - biceps femoris fascia
Positional tendons - infraspinatus
Energy-storing tendons - common calcaneal
What type of collagen predominates in ligaments and tendons?
Type 1
Explain how the collagen fibers of tendons/ligaments change under stress
They show a wavy or crimped appearance when at rest however when under tensile stress they become more aligned and elongated.
Stress relaxation and creep can occur overtime at low load over a long period of time due to interfibrillar sheer.
high stiffness and strength > under longitudinal tensile loads
viscoelastic response in that the rate of loading affects the response
initial phase?
elastic region?
yield point?
initial phase of elongation
toe region = represents straightening of fibrillar crimps.
linear elastic region
recoverable elongation dt fibrillar elongation or interfibrillar shear.
Rapid loading > fibrillar elongation
interfibrillar shear > stress relaxation and creep
Stresses and strains approach the yield point > irreversible disruption of interfibrillar hydrogen bonds and cross-links = permanent distortion of alpha helices.
List the two types of entheses and define each
Fibrous entheses - predominate at sites where muscle attached to diaphyseal bone. Composed of dense bands of Collagen called Sharpeys fibers that merge with the periosteum and penetrate deeply into the cortical bone.
Fibrocartilaginous entheses - Contain a zone of fibrocartilage at the attachment which forms a transition between the collagen fibers of the ligament/ligament and the bone. Periosteum is NOT present
What is a sarcomere?
A contractile unit of a myofibril composed of parallel arrays of overlapping filaments of actin and myosin
What structure is responsible for intracellular calcium sequestration?
The sarcoplasmic reticulum
Describe the process of contraction of the myofibres of a motor unit
Release of ACh from axonal terminal –> binding to sarcolemma –> depolarisation and release of Ca from sarcoplasmic reticulum –> Ca binds to troponin –> conformational change on tropomyosin leading to exposure of the myosin interaction site on the actin filament –> myosin engages adjacent actin –> ATP hydrolysis leading to longitudinal sliding and shortening of the sarcomere
Describe the progressive building blocks of a muscle and its associated surrounding layer
Individual myofibers innervated by terminal branch of motor axon
myofibres surrounded by sarcolemma
muscle fibres surrounded by endomysium
fascicles surrounded by perimysium
muscle bellies surrounded by epimysium
What is a satellite cell?
A undifferentiated, unipotent muscle progenitor cell which resides within the basal lamina adjacent to the plasma membrane of a muscle fibre
List the 2 basic muscle fiber types
Type 1 - slow twitch. Adapted for sustained contraction of low velocity. Rich in mitochondria and fueled by primarily oxidative metabolism
Type 2 - fast twitch. Adapted for more transient high-force, high-velocity contraction. Fewer mitochondria but rich in myofibrils.
Extracellular matrix makes up less than 10% of skeletal muscle, yet it contributes greatly to both the mechanical properties
uscle connective tissue (myofascia) provides the basic structure along which force is transferred from individual contractile units to the tendon and also underlies the elastic properties of muscle.
high-intensity conditioning leads to hypertrophy of type II fibers through synthesis of myofibrillar proteins and enlargement and increased contractile capabilities of myofibers
