CHANGES IN S-YKL-40, S-IL-6 AND CIRCULATING MESENCHYMAL PROGENITOR CELLS IN PATIENTS DURING BONE REGENERATION

Abstract

Summary: Investigation of the specific roles of circulating mesenchymal progenitor cells, YKL-40 and IL-6 during regeneration of planned or traumatic bone traumas.

Introduction: YKL-40 is a growth factor with possible involvement in regeneration of mesenchymal tissue. IL-6 is a pro-inflammatory marker. Mesenchymal progenitor cells (MPC), is a subpopulation of mononuclear cells (MNC), involved in bone regeneration. The aim was to investigate the involvement of YKL-40 in bone regeneration by analysis of the posttraumatic changes in s-YKL-40, s-IL-6, MNC and MPC in patients with planned or traumatic bone traumas.

Materials and Methods: Two cohorts with a total of 50 patients, with either ankle- (Cohort 1: N=13) or hip fracture (Cohort 1: N=10, cohort 2: N=8) or planned hip replacements (Cohort 1: N=9, cohort 2: N=10) were included. Contemporary healthy controls (N=17) were also included. 8 blood samples were taken day 1, 3, 7, 14, 21, 28, 42 and 84 after bone trauma from patients in cohort 1. Patients in cohort 2 had the same blood samples taken, including two additional ones taken 3–5 and 12–15 hours after hip fracture. MNC was counted, Phenotype of MPCs were determined by flow cytometry, s-YKL-40 and s-IL-6 quantified by ELISA.

Results: Changes in MNC, YKL-40 and IL-6 correlated to the magnitude of the traumas, with larger responses in patients with hip fractures or planned hip replacements compared to patients with ankle fractures (MNC: p=0.0006; YKL-40: p=0.0004; IL-6: p< 0.0001). S-YKL-40 further correlated to the type of bone trauma, documented by different levels of YKL-40 in patients with hip fractures or -planned hip replacements, from day 14 to 42 after fracture (Cohort 1: p=0.04; Cohort 2: p=0.005). The posttraumatic changes in YKL-40 and IL-6 did not correlate. Age and number of circulating MNC (p=0.0003, r=−0.61) were inverse correlated. S-YKL-40 correlated positively to a population of circulating cells with a specific phenotype of CD45neg, CD105pos-MNCs (r=0.26, P=0.01) and CD45neg, CD144pos-MNCs (r=0.27, P=0.01). These phenotypes are associated with MPCs. This correlation was only seen in patients with hip fractures.

Conclusions: Circulating MNC, YKL-40 and IL-6 changed posttraumatic according to the magnitude of the trauma. Serum YKL-40 also changed according to the type of bone trauma during early bone regeneration, indicating a pivotal quantitative role for YKL-40 in bone regeneration.

The positive correlation between YKL-40 and circulating CD45neg, CD105pos, CD144pos-MNCs during early ossification in hip fractures is a novel finding, which underlines the important role of these cells and YKL-40 during bone regeneration.