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Question	Answer
What is the organic component of bone?	Collagen
What is the inorganic component of bone?	Hydroxyapatite
What other part of the body is composed of the inorganic component of bone?	The teeth are also composed of hydroxyapatite.
How are the organic and inorganic components of bone structured?	Crystals of hydroxyapatite coat the collagen fibres which lie across one another in a scaffold. The hydroxyapatite binds to fibres rather than 'filling gaps'.
What is a Haversian canal?	The Haversian system runs through bone and provides space for nerves and blood vessels to reach the bone tissue.
Which two types of stem cells are the origins of bone cells?	Haemopoietic and mesenchymal.
List five differences between haemopoietic and mesenchymal stem cells.	Haemopoietic stem cells (HSCs) are continuously renewing, whereas this is not necessarily the case for mesenchymal stem cells (MSCs). HSCs are continuously formed to support the body of cells they differentiate into, whereas mesenchymal stell cells are only formed at certain times. HSCs are short lived whereas MSCs are long lived. HSCs are unicellular and matrix free, whereas MSCs are multicellular and matrix bound. Lastly, once differentiated, HSCs have an inflexible phenotype, whereas MSCs have a plastic phenotype and so can be differentiated based on environmental factors (e.g. transcription factors).
List the six tissue types that can be formed from a mesenchymal stem cell.	Tendon, ligament, muscle, bone marrow, cartilage and connective tissue.
What is the name for an immature bone cell?	An osteoblast.
What is the name for a mature bone cell?	An osteocyte.
What type of immature cell is involved in Ca2+ and vitamin D usage?	Osteoblasts, as these are required for their development.
Which cell type involved in bone remodelling is derived from the haemopoietic stem cell lineage? Exactly what lineage are they from?	Osteoclasts are ultimately derived from haemopoietic stem cells. Once the haemopoietic stem cell has differentiated into its myeloid precursor, it further differentiates to a granulocyte-macrophage precursor. It is the macrophage lineage (CFU-M; colony forming unit - macrophage) that the osteoclast is derived from, which makes sense given that it engulfs and digests bone.
With regard to haemopoietic stem cells, what is the difference between a multipotent progenitor and a committed progenitor?	A multipotent progenitor cell is capable of differentiating into many different types of cells, along more than one lineage, whereas a committed progenitor can only differentiate into one type of cell, or along one particular lineage.
When are osteoclasts considered mature?	When they start to function, as opposed to when they are fully differentiated from haemopoietic stem cells.
In what way are osteoblasts related to osteoclasts?	In function: they oppose each other in that osteoblasts are involved in osteogenesis, whereas osteoclasts are involved in osteolysis. That said, they are parasitic on each other in health, as osteoclasts must clear bone (e.g. damaged) in order for osteoblasts to regenerate it, and this balance is critical.
What is the difference in function in the osteoblast and the osteocyte?	Osteoblasts travel into the collagen framework and secrete this organic bone material (it 'creates' the collagen), whereas the osteocyte get traps in this collagen framework.
What is the network of collagen also known as?	The bone matrix.
Once trapped in the collagen, how do osteocytes communicate with one another?	They are networked together via cytoplasmic extensions called canaliculi.
Which is larger: an osteoblast or an osteoclast?	An osteoclast.
Describe a distinctive feature of an osteoclast.	It has a ruffled border which it uses to migrate along bone.
Why is an osteoclast multinucleate, unlike an osteoblast which has a single nucleus?	An osteoblast is almost fully mature and is functional, whereas an osteoclast is only mature when it starts to function. An osteoclast is formed by the fusion of several to many preosteoclasts, resulting in a single, large, multinucleate cell.
What is the secreted collagen in bone referred to as before mineralisation?	Osteoid.
Once osteocytes are trapped in lacunae, what is their primary function?	They function as mechanosensors, detecting the laying down and breaking of bone, particularly with regard to the micro stress fractures that are generated by the tensile forces of muscle against bone during walking and normal activity. They do this using their canaliculi, and can then use these to communicate to other cells to migrate to the area and strengthen the bone, for instance.
What is the name for the groove/cavity that contains osteoclasts during bone resorption?	Howship's lacunae.
How is an osteocyte lacuna formed?	Osteoblasts form lacunae, and when they mature into osteocytes they become trapped in these. They are joined together by canaliculi.
Numerous extrinsic factors including hormones and growth factors activate osteoblast-specific signalling proteins and transcription factors required for osteoblast differentiation. What is the major transcription factor involved?	Core binding factor alpha 1 (Cbfa1), otherwise known as Runx2.
How does Cbfa1/Runx2 result in osteogenesis?	Runx2 is a major transcription factor in osteogenesis. It binds to osteocalcin, a protein expressed on fully differentiated osteoblasts, and activates it. Osteocalcin is pro-osteoblastic.
Which proteins can upregulate Cbfa1/Runx2 expression?	Bone matrix proteins (BMPs), members of the transforming growth factor - beta family (TGF-β). BMP-2, BMP-4, and BMP-7 are significant in both osteoblast differentiation and in upregulating Cbfa1/Runx2 expression- along with parathyroid hormone and fibroblast growth factor. TGF-β acts on SMAD proteins which transduce this extracellular signal within the cell the upregulate gene expression.
Is Cbfa1/Runx2 sufficient to induce osteogenesis alone?	No.
What are the three main pathways for osteoblast regulation known as?	The Runx2, osterix and WNT pathways.
Does the formation and resorption of bone occur normally, or pathologically?	Both, but in health it occurs in harmony.
Macrophage colony stimulating factor (M-CSF) is pro-osteoclastic. What could this mean during infection?	An increase in M-CSF is not specific to osteoclasts, so in the production of macrophages and/or granulocytes during infection, an increase in osteoclasts may also occur, resulting in increased bone resorption.
How does oestrogen protect against osteoclastic activity?	Oestrogen stimulates the production of osteoprotegerin, which prevents RANKL from binding to RANK by imitating RANK. This prevents osteoclasts from being activated and resorbing bone.
What does RANKL binding to RANK on a pre-osteoclast signal it to do?	It signals the fusion of multiple pre-osteoclasts to form a multinucleated osteoclast, and for this cell to form a 'ruffled' border for migrating along bone and resorbing it.
Where is RANKL derived from?	Osteoblasts.
Other than RANKL binding to RANK, what else is necessary for fusion of multiple pre-osteoclasts? Is this factor sufficient on its own to cause this?	M-CSF is also required to bind to pre-osteoclasts to stimulate their fusion. Without RANK/RANKL it is not sufficient for triggering this.
Put the following in the correct order: 1) PTH binds to receptors on osteoblasts. 2) Bone is resorbed. 3) Serum calcium decrease. 4) PTH released. 5) Osteoblasts express RANKL on surface. 6) Calcium released. 7) RANK/RANKL interaction causes osteoclast maturation and activation. 8) Serum calcium increase. 9) RANKL binds to RANK.	3, 4, 1, 5, 9, 7, 2, 6, 8
How is osteoprotegerin production modulated?	When parathyroid hormone stimulates the expression of RANKL on osteoblasts, it also inhibits production of OPG, creating a higher ratio of RANKL:OPG and producing a pro-osteoclastic environment.
What is the mechanism by which osteoclasts resorb bone?	They secrete HCl and proteases to dissolve the calcified hydroxyapatite and its collagen support.
Which chemical factors influence bone growth?	Growth hormone, insulin-like growth factor, and steroid sex hormones.
Why does damaged cartilage heal slowly?	Because it has no blood supply, so all nutrients, oxygen and perhaps antibodies required for repair must reach the damaged site by diffusion which takes a considerable time.

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