Relationship Between the Dynamics of Telomere Loss in Peripheral Blood Leukocytes From Knee Osteoarthritis Patients and Mitochondrial DNA Haplogroups

Objective: To evaluate the evolution of telomere length from peripheral blood leukocytes (PBLs) in subjects from the Osteoarthritis Initiative (OAI) cohort in relation to the incidence of osteoarthritis (OA), and to explore its possible interactive influence with the mitochondrial DNA (mtDNA) haplogroup.

Methods: Dynamics of telomere sequence loss were quantified in PBLs from initially healthy individuals (without symptoms or radiological signs), 78 carrying the mtDNA cluster HV, and 47 with cluster JT, from the OAI, during a 72-month follow-up period. The incidence of knee OA during this period (n = 39) was radiographically established when Kellgren-Lawrence (KL) score increased from < 2 at recruitment, to ≥ 2 at the end of 72 months of follow-up. Multivariate analysis using binary logistic regression was performed to assess PBL telomere loss and mtDNA haplogroups as associated risk factors of incidence of knee OA.

Results: Carriers of cluster HV showed knee OA incidence twice that of the JT carriers (n = 30 vs 9). The rate of PBL telomere loss was higher in cluster HV carriers and in individuals with incident knee OA. Multivariate analysis showed that the dynamics of PBL telomere shortening can be a consistent risk marker of knee OA incidence. Subjects with nonincident knee OA showed a slower telomere loss than those with incident knee OA; the difference was more significant in carriers of cluster JT than in HV.

Conclusion: An increased rate of telomere loss in PBLs may reflect a systemic accelerated senescence phenotype that could be potentiated by the mitochondrial function, increasing the susceptibility of developing knee OA.