Bone Signaling and

RANKL

Alvian Andriyanto, dr.

Pembimbing:
M. Naseh Sajadi Budi Irawan, dr., SpOT(K)
Background
• Signaling bones
Bone metabolism  balance of formation and bone
resorption
Expression of transcription factors  Bone development
Regulation of mesenchymal cells
Endochondral and intramembranous bone formation
Ossification and bone differentiation
Background
• RANK - RANKL
Regulation of bone formation
• Osteoblast
• Osteoclasts
Bone Metabolism
• Bone function
Protection of internal organs
Reserve calcium
The development of the immune system

• The condition of bone homeostasis

The balance between formation (osteoblasts) and bone
resorption (osteoclasts)
 Osteoblasts

Osteoclasts
Bone Metabolism
• Modeling bone
• Changes in bone form
• Mechanical adaptation
• Carried out by osteoblasts and osteoclasts

• Bone remodeling
• Renew the old bone cells
• Mineral homeostasis
• Maintain bone strength
Bone Metabolism

Remodeling

Modeling
Bone Signaling
• Bone formation
• Recruitment of osteoblasts
• Activation of factors in bone formation
• Shh, Sox9, Wnt, FGF, TGF-b, BMP, PKA, and HIF1a
(Chondrogenesis)
Bone Formation
• Somit  Mesenkim  Sklerotom
• Shh  Sclerotom formation
• Sox9  Differentiation of mesenchymal cells into
chondrocytes
Bone Remodeling
Ostoclast
recruitment

reversal Activation of
phase osteoclasts

Bone
resorption
 Bone Remodeling

• Osteoclast recruitment and activation

• It starts after signaling for remodeling
• Signaling  Hormone (PTH, estrongen) or damage
• Increased PTH  Activation of PTH receptors  Protein kinase
A, C activation  Increased osteoclast differentiation and
activation
• Osteocyte apoptotic cells  TGF-β decreased 
Osteoclastogenesis increased
 Bone Remodeling

• Bone resorption
 Regulation by receptor activator of nuclear factor kB ligand
(RANKL) and osteoprotegerin (OPG)

• RANK-RANKL-OPG System
 Activation of osteoclasts  Hydrogen ion secretion  pH
down  Dissolves mineral component to bone  makes
lantern Howship
Bone Remodeling

• Phase reversal
1. Bone resorption stops  Bone formation begins
2. Lakuna Howship  Mononuclear and pre-osteoblast cells
3. Bone growth factors are excluded  Signaling for bone
formation
4. RANKL production is suppressed
5. Contains reversal cells  Transition to bone formation
process
 RANK / RANKL in Bone
• RANKL
▫ Receptor activator of nuclear factor kappa –B ligand
▫ Expressed by osteoblast
• RANK
▫ Receptor activator of nuclear factor kappa –B
▫ Located on osteoclast precursors and mature osteoclasts
• OPG
▫ Osteoprotegerin
▫ Binds to and inhibits RANKL
▫ Expressd by osteoblasts
▫ Protective against bone loss
 Conclusion

• Signaling
1. The process of bone metabolism
2. Role to RANK-RANKL-OPG system
3. The process of formation and differentiation of bone in the
fetus
THANKS