BMS 124: Calcium/Phosphate Metabolism

Calcium

Mineralized tissue (hydroxyapatite in dentin, bone, enamel and cementum)

Hydroxyapetite

Ca10(PO4)6(OH)2; the form of apatite that is the principal mineral component of teeth, bones, and calculus.

Blood clot formation, cell-cell adhesion, intracellular signaling pathway

What are other calcium functions in the body

Cadherin

A calcium-dependent adherence protein, important in the adhesion of cells to other cells.

Phosphate

Component of phosphorylated metabolites (ATP, UDP glucose, glucose 6 phosphate, creating phosphate etc)

DNA/RNA

Phosphate is found in nucleotides including

Phospholipids

Phosphate is found in ____ in cell membranes

Phosphoenzymes

Phosphate can be found in signaling pathways called ______ like receptor tyrosine kinase

99%

About ___ percent of calcium is located in mineralized tissue

Plasma

The remaining 1% of calcium is found in intracellular and extracellular fluid specifically in the ___

85%

About ___ percent of phosphate is mineralized tissue

Intracellular

Remaining phosphate is ______

700 mg

RDA for phosphate

Hydroxyapatite

A calcium and phosphate salt

Lowest

At pH 7, the calcium phosphate solid with the ______ solubility is hydroxyapetite which means the crystal is very stable

Systemic balance

Ca and P ____ directly impacts oral health, disease and treatment success

Vitamin D

Is crucial for absorbing Ca and P

Tooth development

A child with vitamin D deficiency can have less _____ and higher susceptibility to caries

Bone metabolism

Adults with vitamin D deficiency have bad ______ and can have periodontal disease progression

Enamel

hard, outermost layer of a tooth, hardest substance in body, is almost entirely hydroxyapetite

Enamel, dentin, cementum, alveolar bone

What structures have hydroxyapatite as a primary structural component

Dentin

Primary material found in teeth. It is covered by the enamel in the crown and a protective layer of cementum in the root.

Cementum

Specialized, calcified connective tissue that covers the anatomic root of a tooth.

Alveolar bone

bone that supports and encases the roots of teeth

Intestine

Absorbs calcium and P

Bone

Stores calcium and P

Kidney

Excretes calcium and P

Tight junction, concentration gradient

1) calcium passes through ___ formed by claudin proteins between epithelial cells through ____

Lumen, enterocytes

2.1) Calcium ions (Ca 2+ ) from the intestinal _____ (inside the gut) enter the intestinal epithelial cells (_____) through TRPV6.

Calbindin D9K

2.2) Once inside the enterocyte, calcium binds to a cytosolic calcium-binding protein called _______. This protein acts like a shuttle, safely transporting calcium across the cell's cytoplasm without causing harmful buildup of free calcium.

PMCA1, NCX1

2.3) Calcium is then actively pumped out of the enterocyte to the bloodstream by the plasma membrane Ca2+-ATPase (______) and, to a lesser extent, the sodium-calcium exchanger (_____).

Endocytosis, exocytosis

Calcium could also be transported by

Vitamin D

All of the pathways of calcium is regulated by

VDR, upregulate

The active form of vitamin D, 1,25(OH)2D could bind to ____ (vitaminD3 receptor) and ________ the gene expression of proteins in the three pathways, including TRPV6, calbindin D9k, Claudin2,12,15, PMCA1, NCX1

Diffusion, NTB2b carrier, PIT1/PIT2 carriers

What are the three pathways of phosphate intestinal absorption

Vitamin D, phosphate

In intestinal absorption of phosphate, NPT2b carrier is regulated by _____ and dietary ___ level

Not

In intestinal absorption of phosphate, PIT1/PIT2 carries are ____ regulated

Kidney

Both Ca and Pi are filtered from the blood and then reabsorbed in the ____ (majority are reasoned)

Transporters, Carrier protein, ion channels

In reabsorption, Some ____ or ___ or ____ in the process are also regulated by PTH.

PTH (parathyroid hormone)

Transporter/carrier/channel reabsorption of calcium/phosphate is regulated by

Demineralizing, increase

In bone resorption, Ca Pi resorption is ______ process, which releases Ca and Pi from mineralized tissue (hydroxyapatite) into blood stream and ____ Ca and Pi level in the blood.

Remineralization, decreases

Ca Pi deposition is ______ process, which forms hydroxyapatite in mineralized tissue and _____ Ca and Pi level in the blood.

Deposition

We still use bone remodeling as an example to explain Ca and Pi ______ process.

Osteoprotegerin, prevents,

To keep bone resorption under control, the osteoblasts also secrete _____, which binds to RANKL and ______ it from activating RANK receptors.

Slows

Osteoprotegerin, which binds to RANKL and prevents it from activating RANK receptors. This ____ down the activation of osteoclasts.

Osteoid seam

Following bone resorption, osteoblasts start secreting _____, a substance mainly made of collagen, to fill in the lacunae created by the osteoclasts.

Hydroxyapatite

Calcium and phosphate begin to deposit on the seam, forming ____.

Deposition, remineralization

In the _______ process, Ca and Pi in blood go down and form hydroxyapatite.

Inactive

We could get vitaminD2 or D3 which are the _____ form of vitamin D from our diets.

Skin, sun

Our _____ could produce 7-dehydro-cholesterol and with ____ becomes pre vitamin D3

Liver

The vitamin D will be absorbed into the blood and carried to the

Kidney

In the liver, it will be changed to 25-OH-D with 25-hydroxylase. Then it will be carried to the _____

kidney

In the _____, it will be modified to the active form 1,25-dihydroxycholecalciferol (1,25-DHCC).

VDR

After calcium becomes active from the kidney (1,25-DHCC), it will go in the circulation to bind the _____ and have its biological activities.

PTH (parathyroid hormone)

___ could upregulate 1alpha-hydroxylase, therefore, increase 1,25-DHCC level in the kidney

Plasma, surface

PTH secretion is sensitive to ____ calcium level. It is because the calcium-sensing receptor which is located on the parathyroid cell ___.

G protein, phospholipase C (PLC)

This calcium-sensing receptor is a ____ receptor and it activates ___ pathway.

ER

When the extracellular Ca level is normal or high, calcium binds to the receptor which activate PLC signaling pathway and then release calcium from ___.

inhibits

Increased intracellular Ca2+ level ___ PTH released from the cells.

less, ER

When the calcium level is high, ___ extracellular calcium binds to the receptor, which means calcium remains in the _____

Released

When calcium levels are low, secretory granules bind to the cell membrane and PTH gets ______!

Parathyroid gland

___ could sense the extracellular calcium level by their surface membrane protein (calcium-sensing receptor).

low

When calcium level is __, PTH gets released.

Increased bone resorption

PTH released will release calcium into the plasma called

Increase kidney reabsorption

PTH released will _____ so less calcium is excreted in the urine and more stay in plasma

Increase production of 1,25-(OH)2D

PTH released will ____ which will increase intestinal absorption of calcium and also increase bone resorption

inhibited

When plasma calcium level is too high, PTH release will be ____. Everything reverses. So lower the plasma calcium level.

calcitonin

Parathyroid hormone and vitamin D help increase calcium levels, whereas ___ helps lower them.

parafollicular cells

Calcitonin comes from the ____, or C cells.

above, lowering

If the concentration of calcium in the blood goes _____ the normal range, C cells release calcitonin, _____ blood calcium levels.

Osteoclasts

In the bones, calcitonin binds to the ____ and lowers bone resorption

Decreases

In the kidneys, calcitonin _____ Ca/P reabsorption

Vitamin D

PTH

Calcitonin

decrease

Injury, infection, stress-induced hormones (glucocorticoids), parathyroid hormone, and increased pressure on a bone all _______ osteoprotegerin (OCIF) production by osteoblasts, causing greater differentiation of osteoclasts, more bone remodeling, and more demineralization

PTH, Glucocorticoid

What hormonal factors promote bone resorption

Growth hormones, estrogen/testosterone

What hormonal factors promote remineralization

Vitamin D, Ca/P

What nutritional factor promote remineralization

Pressure on bone, immobilization, sedentary lifestyle

What mechanical factors promote bone resorption

Tension on bone, weight bearing exercise

What mechanical factors promote bone remineralization

Inflammation, acidosis

What medical conditions promote bone resorption

Cytokines

____ associated with the repair of tissues after injury or infection, specifically IL-4 and IL13, inhibit mechanisms that stimulate osteoclast differentiation and bone resorption.

Increase, few

Conversely, growth, anabolic and sex hormones, and tension on the bone, all _____ OCIF production by osteoblasts. ____ osteoclasts develop and bone resorption is decreased.

Orthodontic tooth movement

Applying of orthodontic force to the tooth compresses the PDL.

compression

At the ______ side of the tooth, which appears in the direction of the orthodontic force, bone resorption takes place, carried out mainly by osteoclasts.

Tension

At the _____ side, osteoblasts are responsible for the bone formation process.

True

T/F: vitamin D regulates Ca and P levels in blood

Rickets

refers to insufficient mineralization of osteoid at the growth plate, accompanied by an alteration in the growth plate structure. It manifests clinically as skeletal deformation.

osteoid

Rickets is an insufficient mineralization of _____ at the growth plate, accompanied by an alteration in the growth plate structure. It manifests clinically as skeletal deformation.

vitamin D

____ deficiency is the most common cause of Rickets because it leads to low 1,25-DHCC

1,25-DHCC

active form of vitamin D

1,25-DHCC

Vitamin D deficiency will lower ______ which will cause defects in enamel, dentin, and cementum (rickets)

mineralize

In rickets, Osteoclast activity is normal but the bone does not properly _____.

Supplements

Rickets is treated by vitamin D or phosphate _____, depending on the deficiency.

Osteomalacia

Another name for rickets is

Osteoporosis

Trabecular (spongy) and cortical bone lose mass and interconnections despite normal bone mineralization and lab values (serum (Ca2+ and PO43-).

Increase, decrease

Osteoporosis Most commonly due to ______ bone resorption related to ______ estrogen levels and old age.

menopause

In osteoporosis that occurs at ______, osteoclast activity is over-active and osteoblast activity is reduced.

Bisphosphonates

Treatment of osteoporosis is with ________