title: Dynamics of MMP‑9, MMP‑2 and TIMP‑1 in a rat model of brain injury combined with traumatic heterotopic ossification.
abstract: The present study aimed to detect early changes in the concentration of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase‑2 (MMP‑2) and tissue inhibitor of metalloproteinase‑1 (TIMP‑1) in a rat model of brain injury combined with traumatic heterotopic ossification (HO). A total of 132 male Sprague‑Dawley rats were used to establish the experimental and control groups. Anatomy and sample collection were conducted on postoperative days 1, 2, 3, 4, 5, 6 and 7. Hematoxylin and eosin and immunohistochemical staining were performed for local tissues. MMP‑9, MMP‑2 and TIMP‑1 levels and gene expression level were measured by ELISA and reverse transcription‑quantitative polymerase chain reaction. Radiological investigation of the rat lower limbs was conducted at weeks 5 and 10 following modeling to observe the occurrence of HO. The incidence of HO for rats in the experimental group was higher compared with the control group. The serum MMP‑9 levels of the experimental group were notably higher on postoperative days 5‑7 compared with the control group. The MMP‑9 gene expression of the experimental group was higher on postoperative days 3‑7 compared with the control group. The TIMP‑1 gene expression levels were markedly higher compared with the control group at each time point. Thus, an increase in inflammatory response is closely associated with brain injury, in addition to an increase in the number of inflammatory cells with the incidence of HO. The pathological elevation of MMP‑9 and the altered dynamic equilibrium between MMP‑9 and TIMP‑1 contributed to the degradation, remodeling and calcification of the extracellular matrix, resulting in the induction of osteoblast precursor cells in HO. MMP‑9 is a predictive marker of HO.
authors.affiliation: Department of Orthopedics, Southern Medical University Affiliated Fengxian Hospital, Shanghai 200000, P.R. China.
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Shi
authors.affiliation: Department of Orthopedics, Fengxian Central Hospital Graduate Training Base, Liaoning Medical University, Shanghai 310000, P.R. China.
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Ju
authors.affiliation: Department of Orthopedics, Southern Medical University Affiliated Fengxian Hospital, Shanghai 200000, P.R. China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Xiao
authors.affiliation: Department of Orthopedics, Shanghai Fengxian District Central Hospital, Shanghai 310000, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.affiliation: Department of Orthopedics, Changsha Eighth Hospital, Changsha, Hunan 430000, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Southern Medical University Affiliated Fengxian Hospital, Shanghai 200000, P.R. China.
authors.forename: Ming-Mang
authors.initials: MM
authors.lastname: Pan
authors.affiliation: Department of Orthopedics, Shanghai Fengxian District Central Hospital, Shanghai 310000, P.R. China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Ni
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009999:Ossification, Heterotopic / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9