Macrophage depletion reduces cell proliferation and extracellular matrix accumulation but increases the ultimate tensile strength of injured Achilles tendons

Abstract

Macrophages are present in large numbers and display specific and distinct phenotypes during the various phases of tissue repair. However, their role following tendon injury and during repair has never been investigated. We injected C57BL/6 mice daily for 4 days with liposome-encapsulated clodronate to deplete circulating monocytes/macrophages. Placebo mice were injected with PBS. The left Achilles tendons of the mice were transversely sectioned and sutured using the 8-strand technique. Macrophage accumulation and cell proliferation were significantly lower in the tendons of clodronate-treated mice than in those of PBS-treated mice on days 3 and 7 post-injury. TGF-β1 staining was significantly more intense in the tendons of PBS-treated mice on day 7 post-injury. Edema and the dry mass of the Achilles tendons were also higher in the PBS-treated mice on days 7 and 14 post-injury. No differences in absolute strength and stiffness were observed, but Young's modulus and maximal stress were significantly greater for tendons from the clodronate-treated mice than those from PBS-treated mice after 14 days of tendon repair. Overall, our findings showed that macrophages promote cell proliferation and extracellular matrix accumulation but their presence leads to inferior ultimate tensile strength of the Achilles tendons. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:279-285, 2014. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.