Fas receptor ligation initiates extrinsic apoptotic pathway which through its death domains (DD) binds small adapter molecule Fas-associated death domain (FADD) thus activating caspase-8 (or FLICE, FADD-like interleukin-1β-converting enzyme). The activated caspase-8 further activates caspase-3 and other effector caspases which lead the cell into apoptosis. Apoptosis can at this level be prevented by c-FLIP (cellular FLICE inhibitory protein), attaching to DD.
NFκB transcription factors promote cell growth and differentiation. They are activated usually through phosphorylation of inhibitory proteins IκB by IκB kinases (IKK) upon ligand binding of various receptors (i.e. RANKL on osteoclast lineage cells). In the nucleus, NFκB initiates transcription of inhibitors of apoptosis proteins (IAPs), which inhibit the effector caspase-3. On the other hand, binding of IAPs may be prevented by Smac/DIABLO or serine protease Omi, released from a mitochondria by an apoptotic stimulus.
Mitochondria are involved in the intrinsic apoptotic pathway, initiated by cellular stress and leading to the release of cytochrome c from their internal membrane. Together with Apaf-1 (apoptotic protease activating factor-1), cytochrome c forms an heptameric, caspase-9 activating structure - apoptosome. Cytochrome c release is stimulated by the pro-apoptotic members of the Bcl-2 protein family from the Bax subfamily (i.e. Bid and Bad) which destabilize the outer mitochondrial membrane. Anti-apoptotic members (Bcl-2) prevent the activation and effects of the pro-apoptotic Bax proteins. Bax subfamily members may also activate caspases. On the other hand, caspase-8, cleaves and activates the Bid protein, thus transferring the signal from the extrinsic to the intrinsic apoptotic pathway (especially important in type II cells).

Osteoblast differentiation is induced by several receptors, and leads to the activation of osteoblast transcription factors, including runt-related transcription factor 2 (Runx2), osterix, and Dlx5. Transforming growth factor-β (TGFβ) superfamily members (including bone morphogenetic proteins, BMPs) signal via serine/threonine receptor kinases and phosphorylation of Smad molecules. Phosphorylated Smads bind with the common Smad4 and forming a trimeric structure which is translocated to the nucleus, where they induce transcription of osteoblast genes. TGFβ superfamiliy receptors also signal through mitogen activated protein kinase (MAPK) pathways. Fibroblast growth factor (FGF) receptor signals through cytoplasmatic parts possessing tyrosine kinase domains, activated upon conformational changes induced by ligand binding. They phophorylate and activate MAPK and protein kinase C (PKC).
Wnt ligand binds to a frizzled (FZZ)/low density lipoprotein receptor related protein (LRP) complex, activating the intracellular protein dishevelled (DSH). DSH inhibits the activity of complex protein structure which transports β-catenin to the proteasome, and results in β-catenin accumulation in the cytosol. β-catenin is then translocated to the nucleus where it regulates transcription.
Ephrin (Eph) B4 is expressed on osteoblasts and signals through RhoA GTPase, while EphB2 expressed on osteoclasts signals through PDZ proteins. Interaction of EphB2 and EphB4 couples bone resorption to formation.
Osteoclast differentiation is driven by several transcription factors, including nuclear factor of activated T-cells (NFATc1), Jun and Fos proteins, and NFκB. Receptor activator of nuclear factor (NF) κB (RANK) is a receptor from the tumor necrosis factor receptor (TNFR) superfamily, which is essential for osteoclastogenesis. Binding of its ligand (RANKL) activates various signaling pathways including NFκB, MAPK, c-Jun amino-terminal kinase (JNK), phospholipase Cγ (PLCγ), and phosphatidyl-inositol-3-kinase (PI3K). PI3K signaling links the RANK signaling pathway to the Akt proliferation and survival pathway. Binding of monocyte–colony stimulating factor (M-CSF) to its receptor (c-Fms) is essential for proliferation and survival of osteoclast precursors, and signals via PI3K/Akt and ERK. Additionally, signaling through the immunoglobulin (Ig)-like receptor, involving DAP12 protein or FcRγ activates PLCγ, and induces calcium release, and transcription of osteoclast genes via calmodulin (CaM) and calcineurin.
Yellow arrows point to the components of osteoblast and osteoclast differentiation pathways, which are proposed to be regulated by Fas signaling.