Physiology 3120 Lecture Notes - Lecture 44: Hyaline Cartilage, Intramembranous Ossification, Endochondral Ossification
2 May 2018
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Human Physiology Lecture 44
Bone Physiology
- Bones are regenerative, they modify all the time
o Entire existing skeleton will regenerate/remodel itself within 7 years
- If you treat the skeleton well, the skeleton will be stronger than what you had before
Hormonal Regulation of Calcium Balance
- Kidney can not respond to changes in calcium in the same magnitude as to changes to Na+ and water
because of the poor absorption levels of Ca+ in the GI tract
o Ca++ is not secreted n the kidney and GFR tuned to meet sodium elvels
- Calcium deposits in our bone
o It is carefully controlled by a couple of hormones
- Calcium is VERY important for many things:
o Signaling pathways
o Organ systems
o Etc.
- Parathyroid hormone regulates the level of calcium in the extracellular fluid volume
o Regulate PLASMA level of calcium by conserving calcium from the distal convoluted tubule
o Reabsorb more calcium due to PTH elevating blood calcium levels
- Calcitrol (vitamin D) affects absorption of calcium in the gastrointestinal tract
o Absorb it better in the GI tract
o Vitamin D activated into the form Calcitrol, that affects how much calcium we absorb in the
GI system
o CAN ENHANCE CALCIUM ABSORPTION
- 99% of body calcium is stored in bones
o MOST of the calcium we do have is stored in the bones
o Functional because calcium forms a mineral that is good at strengthening our bone tissue
AND it becomes an easy access point
o If at any point in your life you need to increase plasma calcium levels, PTH will stimulate the
bone to degrade so that the calcium gets released into your blood
o PURPOSE OF STORED CALCIUM: degrade bone to release the calcium is necessary
▪ Hope degradation is not too quick because that can lower bone strength
- Calcium is stored as hydroxyapatite crystals (calcium and phosphate salts) in bone to prevent large
changes in plasma calcium levels
o Calcium combines with phosphate salts and inorganic material will be part of the collagen
matrix of the bone that is formed
o Bone is made up of Type 1 collagen and hydroxyapatite crystal
o Storing calcium in bone prevents large changes in plasma calcium levels – do not want the
calcium too high because it can impact the functioning of the other cells of the body troll
o Formation and dissolution of hydroxyapatite in bone DOES NOT require hormonal signals
BUT the plasma calcium levels in the plasma are regulated by hormonal con
- These crystals also provide bone strength
o INORGANIC COMPONENT OF BONE
- Bone serves more functions than just locomotion and protection of vital organs
o Skeleton serves as an endocrine organ – controls ion balance, participate in maintaining
calcium to ensure everything is functioning properly
- Skeletal system is not just for locomotion but regulates and stores ion levels in the body
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o 99% of body’s calcium and phosphate
Types of Bone Formation
- The bones we have right now are optimal
o Have amazing strength
o Right amount of calcium phosphate
- As you age, things start to slow down
- While you are developing the skeleton of your body, there were 2 ways that the skeleton could form
- Two types of bone formation:
o Endochondral Ossification **most bones form this way
▪ Long bones
▪ In utero it was a cartilage template first that was then replaced by bone tissue
• Bones continue to grow because of the remaining part of the collagen
template
▪ Have a growth plate so the specific bones can become longer
o Intramembranous Ossification
▪ Flat bones (skull bones)
▪ Mesenchymal cells in utero became bone directly – converted into the bone forming
cells, osteoblasts
• Laid down collagen and inorganic matrix (hydroxyapatite)
▪ NO CARTILAGE TEMPLATE
- Bones are categorized by the type of developmental process that forms them
Composition and Organization of Bone
- Bones have different processes they undergo
- Trabecular/spongy bone:
o Has gaps
- Articualar cartilage:
o Not that many cells
o Chondryctes are able to maintain ECM rich in proteoglycans and type 2 collagen
- Osteoarthiritis = destrctuction or fibrillation of the ECM
o Chondrocyte malfunction
o Can get compelte articular cartilage removel when the erosion is VERY bad
o People walking with bone and bone
o NOT AN AGING DISEASE
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Endochondral Bone: Cartilage Template Formation
1. Chondrocytes secrete an extracellular matrix containing Type II collagen (scattered) and
proteoglycans (Aggrecan)
o First form a cartilage template (chondrocytes and matrix secreted)
o Chondrocyte (from mesenchymal stem cells) form ECM (almost identical to articular
cartilage
▪ Mesenchymal stem cells condense together and differentiate into chondrocytes
2. Chondrocytes in the center of the template differentiate to hypertrophic chondrocytes
o Slightly larger chondrocytes – increasing in size and maturing from a chondrocyte
o Chondrocytes begin to run out of resources (oxygen, nutrients) - DIFFERENTIATE INTO
HYPERTROPHIC CHONDROCYTES
3. Hypertrophic chondrocytes secrete type X collagen and less proteoglycans
o Type 10 collagen is found in the hypertrophic regions
o Collagens provide strength
o Proteoglycans provide cushion
▪ Therefore, this ECM has less compression or squishability
4. Localized hypoxia in hypertrophic zone of the template triggers secretion of angiogenic factors
(VEGF)recruitment to hypertrophic chondrocytes
o Chondrocytes have been receiving nutrition from diffusion (oxygen, glucose, etc.)
o At some point hypoxia develops because the template gets too big = localized decrease in
oxygen, can’t get far into the template
o VEGF – vascular endothelial growth factor stimulate the recruitment of blood vessels
o GOOD THING!
▪ Hypoxic and the cells are requiring more oxygen and nutrients, you would want to
deliver blood vessel to the region to provide the proper nutrition to these
metabolically active cells
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Bones are regenerative, they modify all the time: entire existing skeleton will regenerate/remodel itself within 7 years. If you treat the skeleton well, the skeleton will be stronger than what you had before. It is carefully controlled by a couple of hormones. Calcium is very important for many things: signaling pathways, organ systems, etc. Parathyroid hormone regulates the level of calcium in the extracellular fluid volume: regulate plasma level of calcium by conserving calcium from the distal convoluted tubule, reabsorb more calcium due to pth elevating blood calcium levels. Calcitrol (vitamin d) affects absorption of calcium in the gastrointestinal tract: absorb it better in the gi tract, vitamin d activated into the form calcitrol, that affects how much calcium we absorb in the. 99% of body calcium is stored in bones: most of the calcium we do have is stored in the bones, functional because calcium forms a mineral that is good at strengthening our bone tissue.
