Introduction bone metabolism (+ In vitro models for metabolic bone diseases + for mechanical loading) Flashcards
What is the impact of an osteoporotic fracture?
- 7% dependency upon others
- 8% admitted to nursing homes
- Increased mortality
- Prevalence increases with increasing age
What is the impact of a fracture on bone density?
Often, there is bone (density) loss after a fracture.
It is seen that even after the bones have healed, there is still deteroriation of the fractured side of the bone. The non-fractured side (e.g. non-fractured leg compared to fractured other leg) has (alsmost) no deterioration of bone.
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What is the relationship between exercise and bone mass?
- Loading (i.e. force put on bones) increases bone mass
- High peak load (i.e. high impact force on bones such as during gymnastics) is more important than duration.
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What is Wolff’s law?
Bony structures orient themselves in form and mass to best resist extrinsic forces (i.e. form and mass follow function).
Describe the function of the following cells:
- osteoblast
- osteocyte
- osteoclast
- osteoblast → responsible for the formation of bone by synthesizing dense, crosslinked collagen and specialized proteins, which compose the organic matrix of bone.
- osteocyte → type of bone cell commonly found in mature bone tissue responsible for mechanosensing and regulation of bone turnover
- osteoclast → type of bone cell that breaks down bone tissue (critical for maintenance, repair and remodleing of bones) via bone resorption (disassembly and digestion of hydrated protein and mineral by the secretion of collagenase)
Fill in the right word:
Bone mass is determined by the balance between bone … and bone ….
Bone mass is determined by the balance between bone formation and bone resorption.
Explain how the balance between bone formation and resorption determines the amount of bone mass.
There are three types of bone remodeling cycles:
- coupled and balanced bone remodeling → the amount of active osteoblasts (responsible for bone formation) and active osteoclasts (responsible for bone resorption) is equal.
- coupled and unbalanced bone remodeling → the amount of active osteoblasts is less than the amount of active osteoclasts, which results in bone mass loss.
- uncoupled bone remodeling → there are no (or far less) active osteoblasts and there are a lot more active osteoclasts, which results in (massive) bone mass loss → i.e. arrested reversal phase.
Animal models have been used to study the load on bones. Answer the following questions:
- What is more important for bone mass production: duration of loading or the degree of peak forces?
- Does the amount of estrogen affect the effectivity of mechanical loading?
- To what do bone cells (osteocytes) respond? And how do they respond?
- What is the result of axial load?
- Peak forces are more important than duration of load.
- Mechanical loading remains effective after estrogen insufficiency.
- Osteocytes respond to bending laod by the expression of growth factors and cytokines.
- Axial load results in the expression of phosphate homeostasis related genes prior to a bone formation response.
What factors/cells are important for the activation of the following processes?
- Mechanosensing by osteocytes
- Bone remodelling
- Mechanosensing by osteocytes → signaling factors
- Bone remodelling → osteoblasts and osteoclasts
What is mechanosensitivity of bone cells?
Mechanosensitivity of bone cells implies the adaptation of bone (cells) to its mechanical environment.
When obtaining primary bone cells from a patient, how can you identify osteoblasts?
Via staining of the cells with:
- Alkaine
- Phosphatase
- Von Kossa
- Alizarin red
And much more (see picture)
A bone biopsy is performed to extract bone cells (or bone cells are used from surgical waste). Next, pulsatile fluid flow (PFF) is used to study the bone cells (i.e. primary human osteoblasts). What is seen as a reaction to PFF?
Production of NO and expression of prostaglandin.
Besides the production of NO and expression of prostaglandin, what else is seen in bone cells when they are exposed to mechanical loading (via e.g. pulsatile fluid flow)?
Mechanical stimuli may affect local vitamin D metabolism in primary human osteoblasts.
When researching primary human osteoblasts by performing pulsatile fluid flow (PFF), it was found that bone cells respond to PFF by the production of NO and the expression of prostaglandin. What else is seen when studying the bone cells of healthy patients compared to patients with rheumatoid arthritis when PFF is applied?
That PFF prevents the stimulatory effect of rheumatoid arthritis serum on osteoclastogenesis (development of monocytes into osteoclasts) (?)
Regarding induced pluripotent stemcells:
What is the difference between:
- reprogramming
- differentiation
- transdifferentiation
- Reprogramming → changing the identity of the cells by returning adult cells to a stem cell-like state.
- Differentiation → identity of stem cells changes to a differentiated (more specialized) cell.
- Transdifferentiation → conversing one cell type to another cell type.
Fibrodysplasia ossificans progressiva is a rare disorder where throughout life, muscles and tendons gradually change into bones. For this disorder, there is no cure and the only treatment is anti-inflammatory treatment. Researchers performed a study to understand more about this disorder.
Click flashcard to see the conclusion of this study.
Name an example of a dynamic cell culture model.
Name an example of a bone-on-a-chip model.
What are challenges for the development of bone-on-chip models?
