Attenuated synovial fluid ghrelin levels are linked with cartilage damage, meniscus injury, and clinical symptoms in patients with knee anterior cruciate ligament deficiency

Discov Med. 2016 Dec;22(123):325-335.

Abstract

Background: The meniscus injury and post-traumatic knee osteoarthritis (PTOA) following anterior cruciate ligament (ACL) lesions often cause great burdens to patients. Ghrelin, a recently identified 28-amino-acid peptide, has been shown to inhibit inflammation and perform as a growth factor for chondrocyte.

Objective: This study was aimed at investigating ghrelin concentration in synovial fluid and its association with the degree of meniscus injury, articular degeneration, and clinical severity in patients suffering from anterior cruciate ligament (ACL) deficiency.

Methods: 61 ACL deficiency patients admitted to our hospital were drafted in the current study. The Noyes scale and Mankin scores were used to assess articular cartilage damage arthroscopically and histopathologically, respectively. The Lysholm scores and International Knee Documentation Committee (IKDC) subjective scores were utilized to evaluate the clinical severity. The radiological severity of meniscus injury was assessed by MR imaging. Serum and synovial fluid ghrelin levels were determined using enzyme linked immunosorbent assay (ELISA). The cartilage degradation markers collagen type II C-telopeptide (CTX-II) and cartilage oligomeric matrix protein (COMP) in addition to inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also examined. Receiver operating characteristic (ROC) curve was performed and the area under curve (AUC) was calculated to assess the diagnostic value of ghrelin levels for the prediction of the MRI grading for meniscus injury by comparing with other biomarkers.

Results: SF ghrelin levels were positively related to Lysholm and IKDC scores. PTOA patients with grade 3 showed significantly decreased levels of ghrelin in SF compared with those with grade 2. The ghrelin levels in SF were negatively related to MRI signal grades for meniscus injury. SF ghrelin levels were also inversely associated with Noyes scale and Mankin scores, and levels of inflammation markers IL-6, TNF-α, and degradation biomarkers COMP and CTX-II. ROC analysis showed that ghrelin was more valuable for severe meniscus injury diagnosis by MRI imaging.

Conclusions: Synovial fluid ghrelin levels demonstrated an independent and negative association with meniscus injury, cartilage damage, and clinical severity in patients with ACL deficiency. Ghrelin in SF might serve as a potential cartilage protective factor for PTOA. Local application of ghrelin as a potential adjuvant therapy for delaying cartilage degeneration following ACL injury deserves further study.

MeSH terms

  • Adult
  • Anterior Cruciate Ligament Injuries / complications*
  • Anterior Cruciate Ligament Injuries / diagnostic imaging
  • Anterior Cruciate Ligament Injuries / pathology
  • Arthroscopy
  • Biomarkers / analysis
  • Cartilage Oligomeric Matrix Protein / analysis
  • Cartilage, Articular / diagnostic imaging
  • Cartilage, Articular / injuries*
  • Cartilage, Articular / pathology
  • Collagen Type II / analysis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Ghrelin / analysis*
  • Humans
  • Interleukin-6 / analysis
  • Magnetic Resonance Imaging
  • Male
  • Meniscus / injuries*
  • Osteoarthritis, Knee / blood*
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / etiology
  • Osteoarthritis, Knee / pathology
  • Peptide Fragments / analysis
  • Synovial Fluid / chemistry*
  • Trauma Severity Indices
  • Tumor Necrosis Factor-alpha / analysis
  • Young Adult

Substances

  • Biomarkers
  • COMP protein, human
  • Cartilage Oligomeric Matrix Protein
  • Collagen Type II
  • GHRL protein, human
  • Ghrelin
  • IL6 protein, human
  • Interleukin-6
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • collagen II C-telopeptide