Bone Metabolism Continued Flashcards
recall that bone remodeling is a dynamic process that allows for bone growth, fracture healing or liberation of calcium bone stores to ECF. If you can’t remodel bones, it can lead to___
osteopetrosis.
Osteopetrosis, literally “stone bone”, also known as marble bone disease or Albers-Schönberg disease, is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis.
they can’t heal. their trabecular bone gets so dense that they lose hematological processes.
3 key steps of bone remodeling:
- __ of existing bone
- formation of new __
- __
- resorption of existing bone
- formation of new osteoid
- mineralization
process of osteoclasts:
___ bind together to form a giant osteoclast. The bottom surface of the osteoclasts form an __ __ so that the osteoclast can anchor itself to the bone surface.
__ compartment is formed between the surface of the osteoclast where the adhesion ring is, and the bone surface, which is where the site of __ will be. This is called the __ __.
• In the ruffled border, there is __ and __, which allows calcium and bone __ to occur. Forms a crater, the “__ __.”
Osteocytes bind together to form a giant osteoclast. The bottom surface of the osteoclasts form an adhesion rings so that the osteoclast can anchor itself to the bone surface.
Resorption compartment is formed between the surface of the osteoclast where the adhesion ring is, and the bone surface, which is where the site of demolition will be. This is called the ruffled border.
• In the ruffled border, there is acid and hydrolyses, which allows calcium and bone resorption to occur. Forms a crater. “Resorption pit.”
how does the osteoclast know where to go and how does this bone resorption mechanism get started?
- The process of osteoclastic bone resorption is tightly controlled. It is not random at all. These colony forming units, macrophages, express __, which is a transcription factor.
- The osteoclasts have a __ __. They are originally secreted by the __. ___ must be present before the demolition crew gets going. The demolition crew only does its work when the team that will fill in new bone tells them to. The ___ are the ones who send the signal to the __ __ to tell the __ to engage the demolition crew (__) to remove the old bone and then the __ puts in the new bone.
- The process of osteoclastic bone resorption is tightly controlled. It is not random at all. These colony forming units, macrophages, express RANK, which is a transcription factor.
- The osteoclasts have a RANK Ligand. RANK ligands are originally secreted by the osteoBLAST. Osteoblasts must be present before the demolition crew gets going. The demolition crew only does its work when the team that will fill in new bone tells them to. The osteocytes are the ones who send the signal to the bone surface to tell the osteoblast to engage the demolition crew (osteoclast) to remove the old bone and then the osteoblast puts in the new bone.
• How does the osteocyte know where to make new bone?
They have long processes that can sense fracture. If you break a bone and a fracture line severed an osteocyte communication line, it knows where to fix the fracture line.
It can also sense Loading, so that when you are in an upright position requiring strength to the skeleton. When you lift weights, osteoblasts are activated.
Role of osteoprotegerin (OPG) in osteoblast signalling
it acts as a decoy receptor for RANK ligand.
When the osteoblast secretes RANK ligand to get the osteoclast going, it has the ability to secrete OPG which can kind of compete with RANK binding so that the osteoclast doesn’t go overboard. It essentially is a feedback loop.
Osteoclast recruitment, differentiation, and survival all depends on the ___:____ ratio
RANKL: OPG ratio. Many things can influence this ratio and modulate bone resorption
RANKL: OPG ratio is increased by hormones such as ____, which ___ bone resorption
increased by HORMONES like cortisol and cytokines, which INCREASE BONE RESORPTION
RANKL: OPG is influcned by glucocorticoids in the sense that it can incresae ___ and decrease ___ levels, resulting in an ____ in bone resorption
increase RANKL and decrease OPG, resulting in an INCREASE in bone resopriton, since there’s elss OPG to rein in RANKLE
How does estrogen influence the RANKL:OPG relationship?
estrogen increases OPG
After the ruffled border acids and hydrolases releases/resorbs some calcium and bone products, osteoblasts go in and fill in the gap.
- it starts to cluster along the bone surface
- type ___ collagen and other ___ factors are produces, which have both autocrine and paracrine function
- osteoblasts also contain many receptors such as:___, which allows it to be influenced by a number of different hormones. They also contain __ molecules to stay on the site of bone growth.
- it starts to cluster along the bone surface
- type I collagen and other GROWTH factors are produces, which have both autocrine and paracrine function
- osteoblasts also contain many receptors such as:PTH/PTHRP, GH, INSULIN, E2, VITD3, RETINOIDS, which allows it to be influenced by a number of different hormones. They also contain ADHESION molecules to stay on the site of bone growth.
Osteoblasts originaate from ___ ___ cells (endosterum), or ___ stem cells, (periosteum).
- these stem cells proliferate, differentiate into __ and then __, where they start to make the type I collagen and growht factors. when tehy become encaptured in bone, the osteoblasts become __.
- otheres remain as bone lining cells.
Osteoblasts originaate from MARROW STROMAL cells (endosterum), or MESENCHYMAL stem cells, (periosteum).
- these stem cells proliferate, differentiate into preosteoblasts and then osteoplasts, where they start to make the type I collagen and growht factors. when tehy become encaptured in bone, the osteoblasts become osteocytes.
- otheres remain as bone lining cells.
OSTEOBLAST BONE FORMATION is initiatied by __ __ of bone, probably initiataed by the __ .
it can also be initated by _, __.
it can be inhibited by __, __, or malnutrition.
OSTEOBLAST BONE FORMATION is initiatied by mechanical loading of bone, probably initiataed by the osteocytes .
it can also be initated by fracture, hormones.
it can be inhibited by glucocorticoids, immobilization, or malnutrition.
Bones harden through a process of mineralization. Although Ca and PO4 is poorly soluble, they can’t automatically crystalyze because of the absence of ___ ____, as well as their general movement between plasma and ECF.
Vitamin ___ can promote mineralization by ____ Ca xPO4 product.
Mineralization in pH dependent in the sense that an ___ pH promotes mineralization, and an ___ pH increases solubility.
During the process of Nucleation, matrix vesicles budded from the osteoblast surface, deposited in an oriented manner within new osteoid.
Bones harden through a process of mineralization. Although Ca and PO4 is poorly soluble, they can’t automatically crystalyze because of the absence of CRYSTALLIZATION NUCLEI, as well as their general movement between plasma and ECF.
Vitamin D can promote mineralization by CONCENTRATING Ca xPO4 product.
Mineralization in pH dependent in the sense that an ALKALINE pH promotes mineralization, and an ACIDIC pH increases solubility.
During the process of Nucleation, matrix vesicles budded from the osteoblast surface, deposited in an oriented manner within new osteoid.
T/F PTG promotes mineralization
false. PTH cannot promote mineralization (CA x PO4 stays the same)
outline the process of nucelation/crystalization.
The matrix vesicle expresses the __ channel, and ___ phosphate, which bring __ and __ into the vesicle to produce a __ solution. In the correct pH (__) environment without the movement for fldui, the __ __ crystal forms and propagates to form a crystallization structure.
The matrix vesicle expresses the calbidin channel, and alkaline phosphate, which bring calcium and phosphate into the vesicle to produce a supersaturated solution. In the correct pH (alkaline) environment without the movement for fldui, the calcium hydroxyappntitie crystal forms and propagates to form a crystallization structure.
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