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First published on August 8, 2007, doi:10.1177/0363546507305015
This version was published on November 1, 2007
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The American Journal of Sports Medicine 35:1870-1876 (2007)
© 2007 American Orthopaedic Society for Sports Medicine

Effects of Hyaluronan on Cell Proliferation and mRNA Expression of Procollagens {alpha}1 (I) and {alpha}1 (III) in Tendon-Derived Fibroblasts From Patients With Rotator Cuff Disease

An In Vitro Study

Tetsu Yamada, MD*, Masafumi Gotoh, MD, PhD{ddagger},{dagger}, Kenjiro Nakama, MD*, Yasuhiro Mitsui, MD*, Fujio Higuchi, MD, PhD{ddagger} and Kensei Nagata, MD, PhD*

From the * Department of Orthopedic Surgery, Kurume University, Kurume, Fukuoka, Japan, and the {ddagger} Department of Orthopedic Surgery, Kurume University Medical Center, Kurume, Fukuoka, Japan

{dagger} Address correspondence to Masafumi Gotoh, MD, PhD, 155-1 Kokubu-machi, Kurume, Fukuoka 839-0863, Japan (e-mail: gotomasa{at}kurume.ktarn.or.jp).

Background: Hyaluronan (HA) improves postoperative recovery after flexor tendon surgery, preventing postoperative adhesion. However, its influence on the rotator cuff tendon after cuff repair has not yet been clarified in detail.

Hypothesis: Hyaluronan is likely to modulate cell proliferation and mRNA expression of procollagens {alpha}1 (I) and {alpha}1 (III) in tendon-derived fibroblasts in patients with rotator cuff disease.

Study Design: Controlled laboratory study.

Methods: The study subjects were 10 patients with rotator cuff disease, with an average age of 62 years (range, 44–72). Various concentrations of HA (1.0–5.0 mg/mL) were added to monolayer-cultured tendon-derived fibroblasts from these patients. Hyaluronan binding and CD44 expression on the tendon-derived fibroblasts were evaluated by confocal microscopy using fluorescein-conjugated HA and antihuman CD44 antibody (OS/37). Cell proliferation was evaluated by recording changes in cell number. The levels of expression of procollagen {alpha}1 (I) and {alpha}1 (III) mRNA were measured by real-time reverse transcriptase polymerase chain reaction.

Results: Immunofluorescence cytochemistry detected constitutive binding of HA and CD44 expression on the tendon-derived cells. Treatment with various concentrations of HA significantly inhibited cell proliferation and decreased the expression level of procollagen {alpha}1 (III) mRNA, but not that of procollagen {alpha}1 (I) mRNA, in the tendon-derived fibroblasts.

Conclusion: Hyaluronan modulates cell proliferation and the expression level of procollagen {alpha}1 (III) mRNA, but not that of pro-collagen {alpha}1 (I), in fibroblasts from patients with rotator cuff disease.

Clinical Relevance: Postoperative use of exogenous HA may allow the healing of a repaired rotator cuff tendon with minimal adhesion.

Key Words: hyaluronan • rotator cuff disease • tendon-derived fibroblasts • cell proliferation • procollagen production






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