Skeletal physiology Flashcards
What are mesenchymal cells?
precursor cells that will differentiate into chondrocytes or osteoblasts
germ / stem cells
What are chondrocytes?
cells that secrete and maintain the cartilage matrix - squishy (temporary - growth plate and persistent cartilage - articular cartilage + nose, ears)
What are hypertrophic chondrocytes?
enlarged chondrocytes that are terminally differentiated and, mineralize the matrix (very specific matrix secreted - calcium + phosphate)
What are osteoblasts?
immature bone cell that secretes bone matrix
may mature to osteocyte, not always the case
What are osteocytes?
mature bone cell that maintains the bone matrix
entrapped in bone that is being developed, serve as communicator (detect matrix and can signal to other cells whether there is damage, etc)
What are osteoclasts?
multi nucleated cell that secretes acids and enzymes to dissolve bone matrix
-> bone breaking/ resorption
Describe the first 3 steps in the endochondral bone formation
- Start with mesenchymal cells, they condense (cluster together) to trigger to become/ differentiate into chondrocytes
- Chondrocytes secrete an extracellular matrix containing type II collagen (random organization) and proteoglycans (very flexible at this point)
- Chondrocytes in the centre of the template differentiate to hypertrophic chondrocytes (reasoning largely due to hypoxia - when too big, centre has a lack of oxygen - when smaller, nutrients - glucose, oxygen - can simply diffuse to the cells)
* this is the temporary structure forming in utero in regions your bones will eventually be - cartilage template
What are the next steps after the chondrocytes become hypertrophic of endochondral ossification?
- Hypertrophic chondrocytes secrete type X collagen and less proteoglycans (these make template for bone - more stable)
- Hypertrophic chondrocytes secrete angiogenic factors (like vascular endothelial growth factor - VEGF) which recruits blood vessels to the centre of the template - activate the vasculature to invade the tissue
6, Hypertrophic chondrocytes mineralize the surrounding matrix and undergo apoptosis (after they mineralize, they are programmed to die - leave matrix behind)
*Calcium and phosphate are secreted - hydroxyapatite - make up mineralized part of bone
What are the steps following hypertrophic chondrocyte apoptosis of endochondral ossification?
- Invading blood vessels bring in osteoblasts and osteoclasts to this mineralized zone (primary ossification) - this is the middle zone, centre of long bone, what becomes ossified first
- Osteoclasts remove the hypertrophic chondrocyte extracellular matrix
- Osteoblasts replace the cartilage matrix with osteoid (mostly type I collagen - very organized, linear stacks) and then mineralize it (hydroxyapatite - hydrogen and phosphate)
*replacing the matrix, but utilizes the template as starting point - Chondrocytes on either side of the primary ossification centre are actively proliferating (drive the length of the bone - osteoclasts + osteoblasts just come to replace template)
What are the last couple of steps of endochondral ossification?
- Secondary ossification occurs in both condyles (epiphysis) - either end. In humans this mostly occurs postnatally (after birth). Goes through the same process, chondrocytes -> hypertrophic, etc.
- A temporary cartilaginous region between the two ossification centres is called the growth plate (persists only for a period of time of growth - ends at around puberty)
- Articular cartilage is persistent. These chondrocytes continue to secrete type II collagen and proteoglycans (do not become hypertrophic - unless pathologic) - provide cushion to joint
Describe the growth at the growth plate
- chondrocytes closest to osteoid hypertrophy, get bigger to push the chondrocytes further (lengthening)
- very organized, stack up and proliferate in one direction
- how much growth we get (amount of proliferation and how large the chondrocytes get) is mainly genetic - potential may not be realized though due to diet, improper weight bearing - too soon, etc. - more sleep does make more growth.
- chondrocytes closest to osteoid then undergo apoptosis first - bone formation, etc.
Describe intramembranous ossification
- different than endochondral ossification because there isn’t cartilage template formed
- mesenchymal cells condense to differentiate directly into osteoblasts
- osteoblasts secrete matrix containing type I collagen and secrete hydroxyapatite
- bone is formed around existing blood vessels
- entrapped osteoblasts mature into osteocytes - in primary and secondary ossification centres
- osteocytes, also found in endochondral bone, serve to signal about the quality of the surrounding bone to osteoclasts and osteoblasts
Name two different types of bone organization and their differences
- Compact bone - outside portion of skeleton (skull and long bones - outside) - still have movement within the bone, but less flexible
- Trabecular (spongy) bone - looks like hard mesh of bone - allows fluid + blood vessels + osteoclasts and osteoblasts to move throughout - flexible
Describe bone remodelling
- bones have the ability to adjust strength dependent on use
- bone shape can be rearranged if mechanical forces are altered
- bone matrix becomes more brittle with age so a new organic matrix needs to be deposited
- osteoblasts and osteoclasts are coupled in their activity - both get signalled
- bone resorption takes approximately 20 days
- bone formation takes approximately 150 days (3 months)
*Quiescence (or quiescent bone) is areas where nothing is currently occurring
What is osteoperosis?
- can be caused by the imbalance of osteoblasts and osteoclasts activity
- more resorption (faster), less bone formation
- post-menopausal women at greater risk for developing osteoporosis (osteoclasts + osteoblasts controlled by estrogen - estrogen levels drop after menopause)
- get pitting of bones - bone loss
