Bones, Joints and Soft Tissues Flashcards
What type of collagen is found in the bone matrix?
Type I collagen
What specific protein is found in bone?
osteopontin
aka osteocalcin
What type of cell creates osteopontin (osteocalcin) that is found in bone?
osteoblasts
What are the three major functions of osteoblasts?
- CALCIUM HOMEOSTASIS
- bone formation
- mineralization
True or False: osteopontin (aka osteocalcin) is a sensitive and specific serum test that can be done to detect osteoblast activity.
True
What inorganic compound is responsible for a bone’s hardness?
hydroxyapatite
Bones harbor the majority of these two elements in the body.
- 99% of body’s calcium
- 85% of body’s phosphorus
What are the two histologic forms of bone?
Woven: produced rapidly, fetal development, fracture repair; haphazard arrangement of collagen; abnormal finding in adults
Lamellar: slow production, parallel collagen, stronger
What are osteocytes and their main role?
-inactive osteoblasts with decreased cytoplasm that are embedded in the matrix
- control calcium and phosphorus levels
- detect mechanical force and translate it to bioactivity
What are canaliculi in the bone?
-tunnels that osteocyte dendritic processes use to network
What are osteoclasts and their main role?
- MULTINUCLEATED macrophages derived from circulating monocytes
- bone resorption
Describe how osteoclasts perform their bone resorption.
- in the resorption pit, osteoclasts utilize cell surface INTEGRINS to attach which creates a sealed extracellular trench
- secrete matrix metalloproteases (MMPs) that dissolve organic and inorganic bone components
What are the two types of bone ossification?
Endochondral: long bones
-deposits new bone at bottom of growth plate for longitudinal growth
Intramembranous: flat bones
-new bone on preexisting surface for appositional growth
True or False: the adult skeleton is constantly turning over
True; 10% of skeleton is replaced annually
When is peak bone mass achieved?
- early adulthood after cessation of skeletal growth
- 4th decade: resorption > formation leads to decrease in skeletal mass
What is RANK?
–receptor activator for NF-KB on osteoclast precursors
–when stimulated by RANK ligand, it activates NF-KB (a transcription factor) that is essential in generation and survival of osteoclasts that carry out bone breakdown
What is RANKL?
–RANK ligand is expressed on osteoblasts and marrow stromal cells that binds to induce bone breakdown
What is osteoprotegerin (OPG)?
- a “decoy” receptor made by osteoblasts
- binds RANKL
- PREVENT RANKL from interacting w/ RANK
- induces BUILDING of bone
How is WNT/B-catenin involved in bone building and/or breakdown?
–WNT proteins are produced by osteoprogenitor cells and bind to receptors on osteoblasts
–triggers activation of B-catenin and production of OPG (osteoprotegerin)
What is sclerostin?
- -produced by osteocytes
- -inhibits the WNT/B-catenin pathway
What hormones/vitamins promote bone building?
- estrogen
- testosterone
- vitamin D
What hormones/cytokines/substances promote bone breakdown?
- -PTH
- -IL-1
- -glucocorticoids
How is M-CSF (monocyte colony stimulating factor) involved in bone breakdown?
–binding to an M-CSF receptor on osteoclast precursor stimulates tyrosine kinase cascade that generates osteoclasts
How does the breakdown of bones stimulate the formation of bone, in return?
-breakdown liberates/activates matrix proteins, growth factors, cytokines, enzymes (some of which stimulate osteoblasts)
What happens when homeobox proteins are mutated?
-abnormal differentiation of osteoblasts and chondrocytes
What is brachydactyly Type D and E?
- short terminal phalanx of thumb and big toe
- HOXD13 mutation
What are the characteristics of Cleidocranial Dysplasia, an autosomal dominant disorder caused by a RUNX2 mutation?
- patent fontanelles
- delayed closure of cranial sutures
- Wormian Bones (extra bones along cranial sutures)
- delayed eruption of secondary teeth
- primitive clavicles
- short stature
What is the gene mutation in achondroplasia (the most common skeletal dysplasia)?
- FGFR3 gain of fxn (autosomal dominant)
- 90% are new mutations (almost always paternal)
What are the physical characteristics of achondroplasia?
- slow cartilage growth
- short proximal extremities
- NORMAL TRUNK LENGTH
- enlarged head w/ bulging forehead
- depression of the root of the nose
- NORMAL longevity, intellect and reproduction
What is the gene mutation in Thanatophoric Dysplasia (the most common lethal form of dwarfism)?
-FGFR3 gain of fxn
different mutation than achondroplasia
What are the physical characteristics of Thanatophoric Dysplasia?
- -diminished proliferation of chondrocytes
- -disorganization in Zone of Proliferation
- -micromelic shortening of limbs
- -frontal bossing w/ relative macrocephaly
- -SMALL CHEST CAVITY (respiratory insufficiency)
- -bell-shaped abdomen
- -die at birth or shortly afterward
What gene can be mutated that results in abnormal bone density?
LRP5
-depending on the defect, either osteoporosis OR osteopetrosis can be the result
What would a mutation in RANKL cause?
-decreased or absent osteoclasts
What component of connective tissue is abnormal in Osteogenesis Imperfecta (the most common inherited disorder of connective tissue)?
Type I collagen
- -alpha-1 and alpha-2 chains
- -no triple helix formation
What is the least severe type of Osteogenesis Imperfecta?
Type I (most common type)
- normal life span and stature
- childhood fractures, but decrease after puberty
- increased joint mobility
- normal collagen structure, just smaller amount
- blue sclera
- brittle teeth
- hearing loss (in 20’s and 30’s)
What is the most severe type of Osteogenesis Imperfecta?
Type II
- uniformly fatal in utero or shortly after birth
- small stature
- underdeveloped lungs (resp. problems)
- extraordinary bone fragility, intrauterine fractures
What are possible treatments of Osteogenesis Imperfecta?
- surgical “rodding” of long bones
- exercise
- healthy weight
- good nutrition
- no smoking
- no steroids
What mutation causes Osteopetrosis (aka Marble Bone Dz)?
-CLCN7 that encodes proton pumps in osteoclasts
- Carbonic Anhydrase 2 (CA2) deficiency
- -impaired fxn of osteoclasts
- -acidifies the resorption pit and solubilizes hydroxyapatite
–prevents acidification of urine, causing RTA
What is the physical clinical manifestation of Osteopetrosis?
- abnormally brittle bones that fracture easily
- bones lack medullary cavity
- anemia d/t lack of hematopoietic tissue
- bulbous ends of long bones (Erlenmeyer flask)
- nerve compression
Explain the characteristics of the autosomal recessive form of Osteopetrosis vs the autosomal dominant form of the disease.
Recessive: severe infantile; optic atrophy, DEAFNESS, facial paralysis; postpartum mortality d/t fractures, anemia and hydrocephalus
Dominant: mild adult; repeated fractures
In what category are the major of enzymes affected by mucopolysaccharidoses and what types of diseases are they?
- acid hydrolase enzymes
- lysosomal storage diseases
How do mucopolysaccharidoses affect the joints?
- mucopolysaccharides accumulate in chondrocytes and the extracellular space in joints since chondrocytes are a type of mesenchymal cell that normally degrades them
- apoptosis of chondrocytes leading to structural defects in articular cartilage
What can be seen on physical exam of patients suffering from a form of mucopolysaccharidosis?
- short stature
- chest wall abnormality
- malformed bones
What is the difference in bone density between the categories of osteopenia and osteoporosis?
Osteopenia: 1.0-2.5 SD below the mean peak bone mass in young adults
Osteoporosis: at least 2.5 SD below the mean peak bone mass in young adults
What is the main clinical feature that signifies osteoporosis?
- atraumatic fractures
- vertebral compression fractures