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- Title
Trauma-Induced Nanohydroxyapatite Deposition in Skeletal Muscle is Sufficient to Drive Heterotopic Ossification.
- Authors
Moore-Lotridge, Stephanie N.; Li, Qiaoli; Gibson, Breanne H. Y.; Martin, Joseph T.; Hawley, Gregory D.; Arnold, Thomas H.; Saito, Masanori; Tannouri, Sami; Schwartz, Herbert S.; Gumina, Richard J.; Cates, Justin M. M.; Uitto, Jouni; Schoenecker, Jonathan G.
- Abstract
Heterotopic ossification (HO), or the pathologic formation of bone within soft tissues, is a significant complication following severe injuries as it impairs joint motion and function leading to loss of the ability to perform activities of daily living and pain. While soft tissue injury is a prerequisite of developing HO, the exact molecular pathology leading to trauma-induced HO remains unknown. Through prior investigations aimed at identifying the causative factors of HO, it has been suggested that additional predisposing factors that favor ossification within the injured soft tissues environment are required. Considering that chondrocytes and osteoblasts initiate physiologic bone formation by depositing nanohydroxyapatite crystal into their extracellular environment, we investigated the hypothesis that deposition of nanohydroxyapatite within damaged skeletal muscle is likewise sufficient to predispose skeletal muscle to HO. Using a murine model genetically predisposed to nanohydroxyapatite deposition (ABCC6-deficient mice), we observed that following a focal muscle injury, nanohydroxyapatite was robustly deposited in a gene-dependent manner, yet resolved via macrophage-mediated regression over 28 days post injury. However, if macrophage-mediated regression was inhibited, we observed persistent nanohydroxyapatite that was sufficient to drive the formation of HO in 4/5 mice examined. Together, these results revealed a new paradigm by suggesting the persistent nanohydroxyapatite, referred to clinically as dystrophic calcification, and HO may be stages of a pathologic continuum, and not discrete events. As such, if confirmed clinically, these findings support the use of early therapeutic interventions aimed at preventing nanohydroxyapatite as a strategy to evade HO formation.
- Subjects
HETEROTOPIC ossification; SKELETAL muscle; SOFT tissue injuries; ENDOCHONDRAL ossification; MOLECULAR pathology; BONE growth; BONE metabolism; ANIMAL experimentation; BIOLOGICAL models; BONES; CARRIER proteins; COMPARATIVE studies; RESEARCH methodology; MEDICAL cooperation; METAPLASTIC ossification; MICE; RESEARCH; EVALUATION research; OSTEOBLASTS
- Publication
Calcified Tissue International, 2019, Vol 104, Issue 4, p411
- ISSN
0171-967X
- Publication type
journal article
- DOI
10.1007/s00223-018-0502-5