Table 2.

GLP-1 functions and GLP-1R signalling pathways in osteoarthritis.

Healthy conditions	Osteoarthritis conditions	GLP-1 analogues effects	Signaling pathways involved in GLP-1 effects
Homeostasis	Inflammation Cytokines synthesis	Anti-inflammatory (10, 16,30–32, 49–50, 63)	NF-κB PKA/CREB MAPK
Cartilage synthesis Matrix production	Hypertrophic differentiation ER stress	Anabolism/chondrogenic differentiation (43) Anti-oxydative stress (16)	? ? PI3K/Akt MAPK
Cartilage degradation	Catabolism Apoptosis Decreased Autophagy Senescence	Anti-catabolic (ROS, AGEs) Prevent apoptosis (35) ? ?	PI3K/Akt MAPK PI3K/Akt AMPK ? ?
Osteogenesis	Subchondral bone remodeling Osteophytes Reduced mineralization	Proliferation/ Differentiation (62–66) Maturation (69) Migration (63) Autophagy	Erk 1/2 MAPK β-catenin RANKL Wnt/β-catenin ? TGF-β
Adipogenesis	Adipokines synthesis Fatty acid synthesis Inflammation	Proliferation/ Differentiation (75,77) Fatty acid degeneration (47) Anti-inflammatory	PKC ? NF-κB PKA/CREB Erk 1/2
Nociception	Neuro-inflammation Pain Neuronal apoptosis	Neurotrophic/ Neuroprotector (92) Anti-inflammatory (86) Improved pain sensitivity (88) (release of β-endorphin) Analgesic (85) Anti-apoptotic (90)	Erk 1/2 NF-κB PKA/CREB cAMP MAPK Erk 1/2 PI3K/Akt AMPK