Scientists unravel the cause behind osteoarthritis
Researchers have identified a molecular mechanism central to the development of
osteoarthritis (OA), a finding that could pave way for treatment of the painful condition.
"Clinically, scientists have focused on trying to understand how cartilage and joints degenerate in osteoarthritis. But no one knows why it hurts," said Dr Anne-Marie Malfait, from the Rush University Medical Center.
Malfait and her colleagues took a novel approach to unravelling molecular pathways of OA pain in a surgical mouse model exhibiting the slow, chronically progressive development of the disease.
They were able to monitor development of both pain behaviours and molecular events in the sensory neurons of the knee and correlate the data from repeated observations over an extended period.
"This method essentially provides us with a longitudinal 'read-out' of the development of OA pain and pain-related behaviours, in a mouse model," Malfait said.
The researchers assessed development of pain-related behaviours and concomitant changes in dorsal root ganglia (DRG), nerves that carry signals from sensory organs toward the brain.
They found that a chemokine known as monocyte chemo-attractant protein (MCP)-1 and its receptor, chemokine receptor 2 (CCR2), are central to the development of pain associated with knee OA.
Monocyte chemo-attractant protein-1 regulates migration and infiltration of monocytes into tissues where they replenish infection-fighting macrophages. Previous research has shown that MCP-1/CCR2 are central in pain development following nerve injury.
In the study, following surgery the laboratory mice developed mechanical allodynia that lasted 16 weeks. Levels of MCP-1, CCR2 mRNA and protein were temporarily elevated, and neuronal signalling activity increased in the DRG at eight weeks after surgery.
This result correlated with the presentation of movement-provoked pain behaviours which were maintained up to 16 weeks.
According to the Arthritis Foundation, an estimated 27 million Americans live with OA, but, despite the frequency of the disease, its cause is still not completely known and there is no cure.