Cell signaling pathways allow communication between cells through the use of intracellular and extracellular messengers. They are broadly classified as pathways initiated by lipid-soluble messengers, like steroid hormones, or water-soluble messengers, like most hormones and neurotransmitters. The pathways involve messenger binding to receptors which then activates intracellular proteins, resulting in changes in gene transcription, ion channels, or enzymatic activity. This leads to cellular responses like changes in metabolism, secretory activity, or proliferation. In orthodontics, these pathways govern processes like osteoblast differentiation during bone formation and osteoclast recruitment during bone resorption in response to mechanical forces.

1. Preceptors:
Dr. Rakesh Sharma
Dr. Achint Juneja
Presented by: Dr. Tanvi Verma

2. Content
• Definition
• Classification
• Pathways initiated by lipid soluble messengers
• Pathways initiated by water soluble messengers
• Signal transduction in Orthodontics
• References

3. Cell Signalling Pathways
Various diverse events between cell stimulation
and final response are called
SIGNALLING PATHWAYS
They are also known as Signal transduction pathways

5. Receptor
activation
CELLULAR
RESPONSE
Permeability
Metabolism
Secretory
activity
Rate of
proliferation
and
differtiation
Contraction

6. 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

7. 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 factor
Alters the rate of gene transcription
mRNA
tRNA
Protein synthesis

9. Some common Lipid soluble messengers
• Glucocorticoids
activates numerous genes involved in cellular
metabolism.
• Cortisol
inhibit genes whose protein products are
inflammatory mediators.

10. 2. Ligand gated ion channels
• Receptor protein acts as an ion channel
• Seen in;
- Nerve-nerve junctions
- Neuro-muscular junctions

11. Ligand binds
to ion
channel
Opening of
ion channels
Increase
diffusion
across
membrane
Change in
electrical
charge
Cell response
Contraction/
conduction

12. 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.

14. 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

16. 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

17. 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

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

20. 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

21. Cell Signalling
for
an Orthodontist

22. 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)

23. • 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.

24. 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.

25. • 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

27. 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

28. Thank you…