Preceptors: Dr. Rakesh SharmaDr. Achint Juneja

Presented by: Dr. Tanvi Verma

Content

• Definition• Classification• Pathways initiated by lipid soluble messengers• Pathways initiated by water soluble messengers• Signal transduction in Orthodontics

• References

Cell Signalling Pathways

Various diverse events between cell stimulation and final response are called

SIGNALLING PATHWAYS

They are also known as Signal transduction pathways

Receptor activation

CELLULAR RESPONSE

Permeability

Metabolism

Secretory activity

Rate of proliferation and

differtiation

Contraction

Broadly classified as:

Pathways initiated by Hydrophobic messengers

Pathways initiated by Hydrophilic messengers

• Messengers bind to INTRACELLULAR PROTEINS• Eg: Steriod hormone Thyroid hormone Steroid derivatives

• Messengers bind to EXTRACELLULAR PORTIONS of membrane protein• Eg: Most of hormones Neuro-transmitters Paracrine, Autocrine compounds• 4 sub-types:

- Ligand gated ion channels- Intrinsic enzymatic activity- Bounded to janus kinases- G- Protein coupled receptors

1. Pathways initiated by Lipid soluble messenger

Signal enters the cell

Binds with inactive receptor

Activate the inactivated protein/ receptor

Hormone receptor complex

Binds to specific sequence near a gene

Act as transcription factorAlters the rate of gene transcription

mRNA

tRNA

Protein synthesis

Some common Lipid soluble messengers

• Glucocorticoidsactivates numerous genes

involved in cellular metabolism.• Cortisol

inhibit genes whose protein products are inflammatory mediators.

2. Ligand gated ion channels

• Receptor protein acts as an ion channel

• Seen in;- Nerve-nerve junctions- Neuro-muscular junctions

Ligand binds to ion channel

Opening of ion channels

Increase diffusion across

membrane

Change in electrical

chargeCell responseContraction/

conduction

3. Receptors with intrinsic enzymatic capacity

• Generally all enzymatic receptors are TYROSINE KINASE with one exception i.e. GUANYLYL CYCLASE

• Guanylyl cyclase catalyses the formation of cGMP (in cytosol) which in turn acts as a second messenger and then leads to phosphorylation.

4. Cytokines receptors

• There are regulatory proteins• These receptors does not have any

enzymatic activity of their own but their enzymatic action lies in a family of separate cytoplasmic kinases.

• Cascade of phosphorylation leads to cellular response to stimulus

• Mainly involves the Immune system

5. G-protein coupled receptors

• Largest category• G-protein– heterotrimeric protein– 3 sub-units;  alpha, beta, gamma– alpha binds with GDP and GTP– beta and gamma anchor to membrane

First messenger

Change in conformation of G-

protein

Increase affinity for α to GTP α binds with GTP

Dissociates from other sub-units

Activated α binds to other EFFECTOR

PROTEIN

GTPase of α cleaves GTP to GDP

Inactivation of α subunit

Recombining with beta and gamma

units

• Effecter proteins could be- adenylyl cyclase- Phospholipase C- Ion channels- cAMP, cGMP- Ca++

Cell to cell communication is a complex mechanism that has been classified to study

and to understand. A cellular response is generally not because of a single mediator

or messenger but various biochemical processes are involved in transduction

pathways.

These processes are the part of the complex network of communication

that govern basic cellular activities and coordinate the action of cells

Cell Signalling for

an Orthodontist

Osteoblast histogenesis and bone formation

Precursor cells

Osteo-progenitor

G1 pre-osteoblast

G2 pre-osteoblast

osteoblast

Overall Osteoblast differentiation takes about 60 hours (Roberts WE, Morey ER; Am J Anat. 174, 1985)

• G2 pro-osteoblast; D cell is the immediate proliferating progenitor of Osteoblast. (Robert, Mozsary, Klinger: Am J Anat. 165; 1984)• In unstimulated PDL most of the cells are in Go Stage.• This cell reserve gets stimulated under mechanical stimuli.

Osteoclast recruitment and bone resorption

• There is no evidence to suggests that osteoclasts are produced in PDL.

• Their activity is regulated by:- mechanical stimulus- metabolic stimulus

Robert WE, Chase; 1981 showed that metabolic stimuli produces a rapid response of osteoclast but mechanical stimulation produces a slow but more sustained response.

• Pro-osteoclasts are derived from marrow by circulating Promonocytes derivatives. (mechanically controlled)

• Osteoclasts are relatively inert cells, they have few biochemical receptor.

• Local mediators are;- PG- Interleukins- Neuro-secretory agents- Growth factors- Calcitonin

References…

• Orthodontics, current principles and techniques.Graber 5th edition• wiley online library• EJO.oxfordjournals.org• jortho.maneyjournal.org• www.ajodo.org• ncbi.nlm.mih.gov• scholar.google.com• wikipedia

Thank you…