Changes in circulating biomarkers of muscle atrophy, inflammation, and cartilage turnover in patients undergoing anterior cruciate ligament reconstruction and rehabilitation

Am J Sports Med. 2013 Aug;41(8):1819-26. doi: 10.1177/0363546513490651. Epub 2013 Jun 5.


Background: After anterior cruciate ligament (ACL) reconstruction, there is significant atrophy of the quadriceps muscles that can limit full recovery and place athletes at risk for recurrent injuries with return to play. The cause of this muscle atrophy is not fully understood.

Hypothesis: Circulating levels of proatrophy, proinflammatory, and cartilage turnover cytokines and biomarkers would increase after ACL reconstruction.

Study design: Descriptive laboratory study.

Methods: Patients (N = 18; mean age, 28 ± 2.4 years) underwent surgical reconstruction of the ACL after a noncontact athletic injury. Circulating levels of biomarkers were measured along with Short Form-12, International Knee Documentation Committee, and objective knee strength measures preoperatively and at 6 postoperative visits. Differences were tested using repeated-measures 1-way analysis of variance.

Results: Myostatin, TGF-β, and C-reactive protein levels were significantly increased in the early postoperative period and returned to baseline. Cartilage oligomeric matrix protein levels decreased immediately after surgery and then returned to baseline. CCL2, CCL3, CCL4, CCL5, EGF, FGF-2, IGF-1, IL-10, IL-1α, IL-1β, IL-1ra, IL-6, myoglobin, and TNF-α were not different over the course of the study.

Conclusion: An increase in potent atrophy-inducing cytokines and corresponding changes in knee strength and functional scores were observed after ACL reconstruction.

Clinical relevance: Although further studies are necessary, the therapeutic inhibition of myostatin may help prevent the muscle atrophy that occurs after ACL reconstruction and provide an accelerated return of patients to sport.

Keywords: ACL reconstruction; C-reactive protein; cartilage oligomeric matrix protein; muscle atrophy; myostatin; transforming growth factor-β.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Anterior Cruciate Ligament Injuries*
  • Anterior Cruciate Ligament Reconstruction / rehabilitation*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cartilage Oligomeric Matrix Protein
  • Chondrogenesis*
  • Cytokines / blood
  • Extracellular Matrix Proteins / blood
  • Female
  • Follow-Up Studies
  • Glycoproteins / blood
  • Humans
  • Inflammation / blood
  • Inflammation / diagnosis
  • Inflammation / etiology*
  • Insulin-Like Growth Factor I / metabolism
  • Knee Injuries / rehabilitation
  • Knee Injuries / surgery*
  • Male
  • Matrilin Proteins
  • Middle Aged
  • Muscular Atrophy / blood
  • Muscular Atrophy / diagnosis
  • Muscular Atrophy / etiology*
  • Myostatin / blood
  • Postoperative Complications* / blood
  • Postoperative Complications* / diagnosis
  • Postoperative Period
  • Preoperative Period
  • Transforming Growth Factor beta / blood
  • Treatment Outcome
  • Young Adult


  • Biomarkers
  • Cartilage Oligomeric Matrix Protein
  • Cytokines
  • Extracellular Matrix Proteins
  • Glycoproteins
  • MSTN protein, human
  • Matrilin Proteins
  • Myostatin
  • TSP5 protein, human
  • Transforming Growth Factor beta
  • Insulin-Like Growth Factor I
  • C-Reactive Protein