Matrix metalloproteinase-9 is a diagnostic marker of heterotopic ossification in a murine model
ABSTRACT Heterotopic ossification (HO) is a serious disorder that occurs when there is aberrant bone morphogenic protein (BMP) signaling in soft tissues. Currently, there are no methods to detect HO before mineralization occurs. Yet once mineralization occurs, there are no effective treatments, short of surgery, to reverse HO. Herein, we used in vivo molecular imaging and confirmatory ex vivo tissue analyses of an established murine animal model of BMP-induced HO to show that matrix metalloproteinase-9 (MMP-9) can be detected as an early-stage biomarker before mineralization. Ex vivo analyses show that active MMP-9 protein is significantly elevated within tissues undergoing HO as early as 48 h after BMP induction, with its expression co-localizing to nerves and vessels. In vivo molecular imaging with a dual-labeled near-infrared fluorescence and micro-positron emission tomography (μPET) agent specific to MMP-2/-9 expression paralleled the ex vivo observations and reflected the site of HO formation as detected from microcomputed tomography 7 days later. The results suggest that the MMP-9 is a biomarker of the early extracellular matrix (ECM) re-organization and could be used as an in vivo diagnostic with confirmatory ex vivo tissue analysis for detecting HO or conversely for monitoring the success of tissue-engineered bone implants that employ ECM biology for engraftment.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Molecular imaging is used for the detection of biochemical processes through the development of target-specific contrast agents. Separately, modalities such as nuclear and near-infrared fluorescence (NIRF) imaging have been shown to non-invasively monitor disease. More recently, merging of these modalities has shown promise owing to their comparable detection sensitivity and benefited from the development of dual-labeled imaging agents. Dual-labeled agents hold promise for whole-body and intraoperative imaging and could bridge the gap between surgical planning and image-guided resection with a single, molecularly targeted agent. In this review, we summarized the literature for dual-labeled antibodies and peptides that have been developed and have highlighted key considerations for incorporating NIRF dyes into nuclear labeling strategies. We also summarized our findings on several commercially available NIRF dyes and offer perspectives for developing a toolkit to select the optimal NIRF dye and radiometal combination for multimodality imaging.Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 12/2011; 14(3):261-76. DOI:10.1007/s11307-011-0528-9 · 2.87 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Heterotopic ossification (HO) is perhaps the single most significant obstacle to independence, functional mobility, and return to duty for combat-injured veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Recent research into the cause(s) of HO has been driven by a markedly higher prevalence seen in these wounded warriors than encountered in previous wars or following civilian trauma. To that end, research in both civilian and military laboratories continues to shed light onto the complex mechanisms behind HO formation, including systemic and wound specific factors, cell lineage, and neurogenic inflammation. Of particular interest, non-invasive in vivo testing using Raman spectroscopy may become a feasible modality for early detection, and a wound-specific model designed to detect the early gene transcript signatures associated with HO is being tested. Through a combined effort, the goals of early detection, risk stratification, and development of novel systemic and local prophylaxis may soon be attainable.08/2012; 1(8):192-7. DOI:10.1302/2046-3758.18.2000102
- [Show abstract] [Hide abstract]
ABSTRACT: We report a case of isolated ossification of iliopsoas with ankylosis of the left hip in a 27-year-old female. The patient was diagnosed to have Moyamoya disease, a rare chronic occlusive disorder of cerebrovascular circulation following an acute onset of hemiplegia. The patient presented 9 months later to us with ankylosis of left hip which was successfully treated by surgical excision of the heterotopic bone and there was no recurrence at the end of 5 years. A review of literature failed to reveal a similar case with isolated and complete ossification of iliopsoas muscle associated with Moyamoya disease which required surgical intervention. Surgical excision resulted in dramatic improvement in the quality of life. Surgical excision of neurogenic type of heterotopic ossification is a very successful procedure and timely intervention after maturity of mass is very important to prevent the onset of secondary complications and to avoid recurrence.Indian Journal of Orthopaedics 11/2012; 46(6):714-7. DOI:10.4103/0019-5413.104238 · 0.62 Impact Factor