MSCT Week 1: Connective Tissue, Cartilage and Bone Flashcards
The stroma
structural support and connecting framework provided by connective tissue
ECM AKA
Extracellular Matrix
Ground Substance AKA
ECM
Ground substance consists of?
represents a combination of collagens, noncollagenous glycoproteins, and proteoglycans surrounding the cells of connective tissue
The resident cell of connective tissue is?
The fibroblast which is responsible for the production and maintenance of the ECM
Immigrint cells to the connective tissue include…
- macrophages
- mast cells
- plasma cells
has an important role in immune and inflammatory responses and tissue repair after injury
connective tissue
types of connective tissue proper

Types of specialized connective tissue
4 listed

Where is loose connective tissue typically found?
surrounding blood vessels, nerves, and muscles
Identify


Dense connective tissue contains more _________ than _____________.
- fibers
than
- Cells
Loose connective tissue contains more _________ than _____________.
- Cells
than
- Fibers
When the collagen fibers are preferentially oriented as in tendons, ligaments, and the cornea the tissue is?
Dense Regular connective tissue
when collagen fibers are randomly oriented as in the dermis of the skin and wall of the intestine the tissue is called?
Dense irregular connective tissue
Dense _______ connective tissue is poorly vascularized.
Regular
Identify

Dense regular Connective Tissue

Identify

Dense irregular connective Tissue

Glycosaminoglycans AKA
GAGs
GAGs AKA
Glycosaminoglycans
Glycosaminoglycans are?
- long unbranched polysaccharides consisting of repeating disaccharide units
- Thes molecules are highly negatively charged and associate with large amounts of water to create hydrated gels with high viscosity and low compressibility
Glycosaminoglycans charge
Glycosaminoglycans are highly negatively charged and associate with large amounts of water to create hydrated gels with high viscosity and low compressibility
Glycosaminoglycans of physiological significance
6 Listed
- hyaluronic acid
- dermatan sulfate
- chondroitin sulfate
- heparin
- heparan sulfate
- keratan sulfate
What are these?


Proteoglycans are?
constitute a family of macromolecules composed of a protein core to which at least one glycosaminoglycan is covalently bound
the simplest proteoglycan is?
Decorin

What is this?

A proteoglycan (specifically aggrecan)
Proteoglycan charge
highly negatively charged molecules
Proteoglycan function
these molecules help to organize and stabilize the matrix by interaction with other molecules
&
because of their negative charge create a barrier to the passage of positively charged molecules
Proteoglycans are found where?
a component of the basal lamina of epithelial cells and because their negative charge create a barrier to the passage of positively charged molecules
What are these?

Adhesive Glycoproteins
Adhesive Glycoproteins functions
2 Listed
- a component of the ECM of some tissues to help to faciliate the attachment of cells to the ECM
- also involved in affecting the growth, survival, morphology, differentiation and motility of cells
Well-known Adhesive Glycoproteins
- Laminin
- Fibronectin
Adhesive Glycoproteins signature bonds
- disulfide-bonded subunits
&
- have binding sites for cells and other components of the ECM
The most abundant proteins found in the animal kingdom
Collagen
Major protein of the ECM?
Collagen
There are at least ____ types of collagen
28
describe the structure of collagen…
- three collagen α-chains associate in a characteristic right-handed triple helix to form the collagen molecule

Collagen α-chain Amino Acid sequence
each α-chain has a characteristic amino acid sequence where every third amino acid is glycine that allows for the proper formation of the triple helix
Individual collagen molecules associate with one another to form higher-ordered structures called…
collagen fibers
Collagen biosynthesis steps
5 listed

Mutations of the collagen gene, propeptidases or the lysyl oxidase enzyme can lead to the formation of?
abnormal collagens and a variety of musculoskeletal diseases
abnormal collagens arise from mutations in?
3 listed
- collagen gene
- propeptidases
- lysyl oxidase enzyme
Priniciple cell type of collagen
Chondrocytes
Cartilage is typically surrounded by?
fibrous connective tissue layer called perichondrium
Perichondrium contains
stem cells that differentiate into chondroblasts which eventually give rise to chondrocytes
How does cartilage receive nutrition?
diffusion through the ECM because cartilage is avascular
Cartilage grows by 2 mechanisms
2 Listed
- interstitial growth by the division of existing chondrocytes within the cartilage
- appositional growth by the production of new chondroblasts and chondrocytes at the surface of the cartilage from the stem cells in the perichondrium
Types of cartilage
3 Listed
- Hyaline Cartilage
- Elastic Cartilage
- Fibrous Cartilage
Hyaline cartilage attributes
- Avascular (heals poorly)
- surrounded by a perichondrium
- chondrocytes surrounded by a matrix of Type II collagen, proteoglycans and
- water provides the compressive strength of hyaline cartilage and moves freely in and out of the matrix in response to compressive stress (this is important for the deformation of cartilage and exchange of nutrients and waste products)
Hyaline cartilage is found
3 listed
- in the skeleton of the embryo
- articular cartilage in joints
- cartilage of the respiratory tract
Identify

Hyaline Cartilage

Elastic Cartilage Attributes
3 listed
- avascular (heals poorly)
- Surrounded by perichondrium
- chondrocytes surrounded by a matrix of type II collagen, proteoglycans and elastic fibers
Elastic Cartilage found?
2 listed
- External ear
- epiglottis
Identify

Elastic Cartilage

Fibrous Cartilage Attributes
3 Listed
- Avascular (heals poorly)
- No perichondrium
- chondrocytes surrounded by a matrix of Type I collagen. resembles dense connective tissue
Fibrous Cartilage found
found in the intervertebral discs, menisci of the knee, pubic symphysis
Identify

Fibrous Cartilage

Bone ECM
the ECM has become impregnated with calcium salts and phosphate by a process called mineralization
Bone Vascularization
Bone is highly vascularized and very metabolically active
Primary functions of bone
3 Listed
- provide attachment sites for muscles
- protect the soft tissue organs in the body
- serve as a reservoir for calcium and phosphate ions
Bone is constantly …
remodeled and reshaped in response to physical stresses and the mineral needs of the body
ECM of bone contains
organic and inorganic components
Organic Matrix of bone AKA
Osteoid
Osteoid AKA
Organic matrix of bone
Osteoid is composed of?
is primarily composed of type I collagen and proteoglycans
Three non-collagenous glycoproteins in osteoid
3 listed
- osteocalcin
- osteopontin
- osteonectin
Inorganic matrix of bone AKA
Bone mineral
Bone Mineral AKA
Inorganic bone matrix
Inorganic matrix of bone consists of
Calcium and phosphate salt called hydroxyapatite
Hydroxyapatite
bone mineral of calcium and phosphate salt
99% of the body’s store of Ca2+ is found in
Inorganic matrix of bone as hydroxyapatite
Bone inorganic matrix main function
contributes to the strength and rigidity of bone
Identify

osteoid or organic matrix of bone
Identify

inorganic matrix
collagen fibers covered with inorganic matrix
Identify

H&E stained section of bone

Identify


Identify


Identify


Location of osteoprogenitor cells
periosteal covering of the bone

____________ are derived from Osteoprogenitor cells?
Osteoblasts
Osteoblasts functions
2 Listed
- the main bone-forming cells that actively deposit osteoid along the osteoblast-bone interface
- initiate and control the mineralization of the osteoid
In electron micrographs, osteoblasts display the typical features of cells actively engaging in
3 Listed
- protein synthesis
- glycosylation
- secretion
Features such as an extensive rough ER
Osteoblasts express several proteins important in their function
9 Listed
- Parathyroid hormone receptor
- Alkaline phosphatase
- Vitamin D3
- IGF-1 Receptor
- Type I collagen
- Osteocalcin
- Osteopontin
- Osteoprotegerin (OPG)
- RANKL
Osteoblast: Parathyroid hormone receptor
stimulation of the receptor by PTH induces RANKL and mCSF expression and inhibits OPG production by the osteoblast
Osteoblast: Alkaline Phosphatase
a cell surface enzyme that produces high levels of phosphate ion during bone matrix synthesis
an important metabolic marker of bone formation
Osteoblast: Vitamin D3
Regulates expression of osteocalcin a protein with high binding affinity for hydroxyapatite
Osteoblast: IGF-1 Receptor
2 Listed
- Binds IGF-1 produced by the liver and stimulates the growth of the long bones
- Stimulates osteoid production
Osteoblast: Type I Collagen
The major component of the osteoid matrix
Osteoblast: Osteocalcin
a non-collagenous protein required for bone mineralization
Osteoblast: Osteopontin
A non-collagenous protein that mediates the interaction of osteoclasts with bone surface
Osteoblast: Osteoprotegerin
(OPG)
- a non-collagenous protein that functions as a decoy receptor for the RANKL and inhibits osteoclastogenesis
Osteoblast: RANKL
A ligand for the RANK receptor present on osteoclast precursors and a receptor for OPG
Identify

Osteoblast

The first bone matrix produced by the osteoblast is referred to as…
Primary or woven bone
Primary or woven bone characteristics
characterized by a matrix containing loose randomly oriented collagen fibers and low amounts of hydroxyapatite
Identify



Primary woven bone is subsequently remodeled into
secondary or lamellar bone
Secondary or lamellar bone is characterized by…
organized sheets of collagen fibers (lamella) and high amounts of hydroxyapatite

Osteocytes come from?
when bone formation is completed, osteoblasts flatten out and transform into osteocytes embedded in mineralized bone matrix
Osteocytes are?
highly branched cells with their cell body occupying small spaces or lacunae within layers of the bone matrix
Canaliculi
small channels that course through the bone matrix and interconnect neighboring lacunae
Cell processes of adjacent osteocytes are found within canaliculi and form ____________ with adjacent cells
gap junctions
Osteocytes get nutrients by
extracellular fluid containing nutrients, calcium and other substances diffuse through the canaliculi into the lacunae to support osteocytes
Lifespan of osteocytes
provided osteocytes has access to sufficient nutrients their lifespan can be many years
Osteocytes and bone remodeling
osteocytes respond to forces on the bone and release factors that can stimulate bone remodeling or turnover

Osteocytes
Osteoclasts are
Osteoclasts are large multinucleated cells whose primary function is to degrade the bone matrix
Osteoclasts are derived from…
monocyte precursors originating in the bone marrow
Osteoclastogenesis steps
6 listed

Howship’s Lacuna AKA
Resorption pit
the osteoclast contains high levels of
Carbonic anhydrase II
Carbonic Anhydrase II
an enzyme that generates high levels of hydrogen ions from CO2 and water
How do osteoclasts resorb bone?

Osteoclasts exchange Bicarbonate ions for? and why?
Chloride ions at the apical surface of the cell to prevent an excessive rise in intracellular pH
Osteoclasts release these enzymes and others into the resorption pit
Cathepsin K and matrix Metalloprotease 9
Osteoclast binding of calcitonin
released from the thyroid gland in response to high Ca2+ levels, inhibits the activity of osteoclasts and causes its release from the bone surface


Cortical Bone AKA
Compact bone
Trabecular bone AKA
Cancellous bone

Cortical/Compact bone properties
- osteocytes present in lacunae and the bone matrix are arranged into cylindrical structures called osteons
Osteon
- contains a central canal or Haversian Canal surrounded by 4-10 concentric layers (lamellae) forming connections among all of the lacunae and central canals
- in the central of the Haversian canal is a small blood vessel
__________ are being continuously remodeled by Osteoclasts
Osteons
Identify


Trabecular/cancellous Bone Properties
- Microscopically cancellous bone contains layers of lamellae that form the bony trabeculae that project into the marrow cavity
- there are no osteons in trabecular bone
- Osteocytes are interspersed randomly throughout the trabeculae and in growin bone, the surface trabeculae are often covered with osteoblasts and osteoclasts in the process of remodeling
Identify

