Circulating cellular senescence biomarkers in persons with chronic knee osteoarthritis pain: An exploratory study.

The study sample consisted of middle-to-older-aged adults with a notable prevalence of high-impact chronic knee pain and moderate-to-severe radiographic OA.

• 169 participants aged 45-85 years were included from a larger multi-site study
• 35.5% of participants reported high-impact chronic knee pain
• 27.8% of participants exhibited moderate-to-severe radiographic OA
• Pain impact was defined as the extent to which pain interferes with daily functioning
• Radiographic OA severity was assessed using Kellgren-Lawrence (KL) grade

Hierarchical cluster analysis identified distinct radiographic OA-pain phenotypes based on combined pain impact and radiographic OA severity.

• Cluster analysis was used to empirically identify OA-pain phenotypes
• Phenotypes were defined by combining pain impact scores and Kellgren-Lawrence grade
• Identified phenotypes included groupings such as early ROA with high-impact pain and early ROA with low-impact pain
• A no-pain/no-ROA phenotype group was also identified among the clusters

GDF-15 levels were significantly elevated in non-Hispanic White females with early radiographic OA and high-impact pain, with race- and sex-dependent differences.

• GDF-15 showed significant associations with OA-pain phenotypes specifically in non-Hispanic White females
• Elevation of GDF-15 was observed in the early ROA and high-impact pain phenotype group
• Differences in GDF-15 were dependent on both race/ethnicity and sex
• GDF-15 is a member of the senescence-associated secretory phenotype (SASP) markers assessed

Activin-A levels were higher in non-Hispanic Black participants without pain or radiographic OA and varied by sex in early ROA/low-impact pain phenotypes.

• Activin-A showed race-dependent differences, with elevated levels in non-Hispanic Black participants in the no-pain/no-ROA phenotype
• Sex-dependent variation in Activin-A was observed within early ROA/low-impact pain phenotype groups
• Activin-A was one of four plasma SASP markers quantified from whole blood samples
• Findings suggest Activin-A associations with OA-pain phenotypes are context-dependent by demographic factors

Osteopontin levels were elevated in males compared to females within the same OA-pain phenotype group.

• Osteopontin demonstrated sex-dependent differences in circulating levels
• Males had higher Osteopontin levels than females within the same phenotype group
• Osteopontin was one of four plasma SASP markers quantified
• Samples were collected from whole blood and plasma levels were quantified

IL-15 levels showed no association with radiographic OA-pain phenotypes but were higher in males and positively correlated with age.

• IL-15 did not significantly associate with the empirically derived OA-pain phenotype clusters
• IL-15 levels were higher in males compared to females
• IL-15 showed a positive correlation with age across participants
• IL-15 was one of four plasma SASP markers assessed alongside GDF-15, Activin-A, and Osteopontin

The study assessed four circulating SASP markers from plasma in the context of chronic knee osteoarthritis pain as an exploratory investigation.

• Four SASP markers were quantified: GDF-15, Activin-A, Osteopontin (OPN), and IL-15
• Plasma levels were quantified from whole blood samples
• Participants were a subset from a larger multi-site study
• The study was characterized as exploratory in nature
• The senescence-associated secretory phenotype (SASP) was hypothesized to be associated with distinct OA-pain phenotypes defined by pain impact and radiographic OA severity