Vitamin D and Phosphorus Flashcards
(28 cards)
What are the two types of bone?
Compact/cortical - 80%
cancellous/trabecular - 20%
Osteoblast development
- Stem cell will be exposed to many signals and chemicals which will convert it to a pre-osteoblast
- With the right signals, it gets converted into a osteoblast
- It can get stuck in the bone and become an osteocyte. Also can become a lining cell
Osteoblast has a common precursor with?
Adipocytes
Bone cells
- Osteoprogenitor cells: Contribute to maintaining the osteoblast population and bone mass, from periosteum and bone marrow
- Osteoblasts: Synthesize the bone matrix on bone forming surfaces, from mesenchymal progenitor cells, uninucleated
- Osteocytes: Organized throughout the mineralized bone matrix, support bone structure and serve as mechanosensors, formed from osteoblasts, uninucleated
- 90% of the bone cells are osteocytes
- Lining cells: Line the surfaces of bone, quiescent osteoblasts, uninucleated
- Osteoclasts: Resorb the bone matrix, from hematopoietic / monocyte/macrophage precursor, multinucleated
Which bone cell is the master controller of bone turnover?
Osteocytes. They sense the stress and force on bones. They have a half life of 25 years.
Osteocytes
they are a series of fused cells (dendrites)
they communicate and regulate the bone building.
What are key signals from osteocytes?
Sclerostin, DMP1, Phex, FGF23.
Summary of Osteocytes
- Master regulator of skeletal activity
- Only permanent resident bone cell population
- During development changes from cuboidal cell to dendritic cell
- Most abundant cell in bone (90-95% of bone cells) – surface area 100 times greater than trabecular bone
- Integrates mechanical and chemical signals
- Sense stimuli and regulate effector cells (osteoblasts and osteoclasts
- Are coupled to the environment they inhabit
- Cell-cell contact via gap junctions
- Direct tethers to lacunae wall (proteoglycans)
- Play an endocrine role in controlling P homeostasis
Timeline for remodeling bone?
28 weeks.
The building process is longer than the resorption.
BMU Bone Modeling Unit (3 stages)
•Activation
o Rank and Rank L
o Pre-osteoclast expresses Rank (it is a receptor)
o Rank –L (from the osteoblast) binds to Rank to convert pre-osteoclast to osteoclast.
•Resorption
o Osteoclast causes the bone to break down.
o Osteoclasts die.
•Formation
o Osteoblast are activated.
o Osteoid is unmineralized bond.
o Some of the osteoblasts get stuck in the bone.
o Some get stuck on the lining.
Difference between osteopetrosis and osteoporosis.
osteopetrosis - excess OB
osteoporosis - excess OC
Fibrodysplasia Ossificans Progressiva
normal tissue or normal organ becomes another by destroying first tissue / organ and replacing it with another (phenotypic reassignment)
- Cells that should turn into muscle turn into bone
What bone cells live the longest?
Osteocytes
Hematopoietic precursor cells give rise to?
Osteoclast
What is the decoy receptor to OB on macrophages?
OPG
What is the most metabolically active bone tissue?
Spongy (trabecular)
Calcium, P, and vitamin D interaction
when calcium is conserved, P is excreted. The P stimulates FGF23 to deal with PTH (look at diagram)
Phosphorous
- Ubiquitous in body; DNA / RNA/ phospholipids / phosphorylation of many enzymes, proteins and sugars
- Integral component of ATP
- Integral component of bone
Phosphorus homeostasis
- Goal to maintain serum calcium-phosphate product at level needed for mineralization of bone
- Too high – hyperphosphatemia
- Premature calcification of the vasculature
- Death due to cardiac events
- Too low – hypophosphatemia
- Muscle dysfunction / weakness
- Low cardiac output from respiratory muscle weakness
- Mental status changes / cell membrane instability (low ATP)
P Absorption
- Absorption ranges 65-90% in infants and decreases to about 50-70% in adults
- Whereas calcium is about 30%
- Most occurs in small intestine by load-driven passive absorption
- Transcellular (through) or paracellular (around)
- Active absorption (in the enterocyte) via sodium-phosphorus cotransporters (NAPi-2b or NPT2B) and PiT1
- Calcitriol increases NaPi-2b cotransporters in intestine
- Can absorb P without D
- ***P absorbed with 70% efficiency – Ca absorbed with 30% efficiency – need separate mechanism to remove excess P released from PTH-mediated bone resorption
Phosphorus – Urinary Excretion
- Major regulator of systemic P economy
- 95% reabsorbed in PCT (proximal convoluted tubule)
- Highly regulated in response to dietary P intakes
- NaPi-2a (NPT2A) and NAPi-2c (NPT2C) in kidney → key transporter
- Kidney responds to PTH, FGF23 and Pi concentrations
Speculative Public Helath Link of Excess P
- FGF23 will inhibit PTH
- Decreased renal sytntehsis calcetriol
- Interfere with TG synthesis
- Plaque formation, heart attack, etc
- Insulin resistance → Type 2 diabetes
- Tumor promotion
Hormones and regulation of Phosphorus
- 1,25(OH)2D – increase bone resorption (P release)
- PTH –
- Lowers renal P threshold = Plasma P concentration above which phosphate begins to appear in the urine
- Inhibits proximal tubular phosphate reabsorption
- Lowers serum P within MINUTES of giving hormone to humans
- FGF23 = Phosphatonin; A phosphatonin is a PTH-independent factor that regulates P metabolism
- FGF23, FGF7, secreted frizzled related protein-4 (sFRP-4), matrix extracellular phosphoglycoprotein (MEPE)
- Made from osteocytes
FGF23
- Made by osteocytes; bone is an endocrine organ for regulation of P metabolism
- Binds to FGFR and Klotho
- Goal to rid excess P released into circulation from bone resorption
- Reduces P reabsorption by the kidney by withdrawing NaPi transporters on the apical membrane
- Reduces calcitriol (active vitamin D) production; indirectly reduces P absorption
- Might act on PTH grand to suppress PTH transcription
