801: Mechanotransduction and Epigenetics

osteoblasts, mast cells, red blood cells, and neurons are examples of things that have the same DNA but specialize based on order

cells

a group of cells organized for a common purpose

tissues

what are the 4 main types of tissues

epithelium, connective, muscle, nervous

a group of tissues organized for a common purpose

organs

a group of organs organized for a common purpose

organ system

a collection of organ systems grouped for a common person

organisms

how connective tissue proper responds to mechanical forces

mechanotransduction

as tendons are placed under tension, tenocytes experience what?

- compression and shear forces through its link to collagen bundles and tension in the direction of the tensile load

the intracellular calcium concentrations coming in from the stretch activated ion channels regulate what?

- intracellular signaling
- action polymerization
- cytoskeletal remodeling
- cell motility

the mechanosensitive tenocyte has specific transcriptional responses to what?

- underloading
- overloading
- physiologic loading

what decreases the expression of the extracellular matrix including proteins, collage, and aggrecan?

underloading

what increases the expression of proinflammatory cytokines like prostaglandin?

overloading

cytoskeletal stresses might be directly transduced into what?

nuclear function and gene expression

what reorganizes when stress is applied to the cell?

chromatin

what is chromatin?

densely packed strands of DNA

tightly wound DNA with deacetylated chromatin does what to genes

turns them off

open or loosely wound DNA, acetylated chromatin does what to genes

turns them on

learned behavior carried on to future generations

epigenetics

cells will respond differently to what?

- the type of load (shear, compressive, tensile)
- magnitude of load
- duration of load
- frequency of load

cells can do what in response to the loads they experience?

up regulate and down regulate transcriptional responses

process by which DNA is unwound and a specific segment of DNA, a gene, is copied to a messenger RNA (mRNA) an transported to the cytosol

transcription

process by which transfer RNA (tRNA) facilitate the machine process from mRNA to amino acids which are then sequentially linked to a protein

translation

what are the chief factors in cell behavior?

proteins

what in a protein provides functional specificity?

their amino acid sequence

mechanical factors can directly alter what? how?

nuclear transport; because mechanical forces alter the transport of transcription factors and calcium across nuclear envelop

forces applied to the extracellular matrix can travel to what? via what?

to integrin-anchored focal adhesions via matrix connections and cytoskeleton filaments (actin)

Cell adhesion molecules offer what?

communication between cells

explain the movement loading curve in response to tissue health

- immobilization leads to poor tissue health
- chronic loading leads to poor tissue health
overall: there is an optimal amount of movement and loading to give the best tissue health