title: Local manganese chloride treatment accelerates fracture healing in a rat model.
abstract: This study investigated the effects of local delivery of manganese chloride (MnCl2), an insulin-mimetic compound, upon fracture healing using a rat femoral fracture model. Mechanical testing, histomorphometry, and immunohistochemistry were performed to assess early and late parameters of fracture healing. At 4 weeks post-fracture, maximum torque to failure was 70% higher (P<0.05) and maximum torsional rigidity increased 133% (P<0.05) in animals treated with 0.125 mg/kg MnCl2 compared to saline controls. Histological analysis of the fracture callus revealed percent new mineralized tissue was 17% higher (P<0.05) at day 10. Immunohistochemical analysis of the 0.125 mg/kg MnCl2 treated group, compared to saline controls, showed a 379% increase in the density of VEGF-C+ cells. In addition, compared to saline controls, the 0.125 mg/kg MnCl2 treated group showed a 233% and 150% increase in blood vessel density in the subperiosteal region at day 10 post-fracture as assessed by detection of PECAM and smooth muscle α actin, respectively. The results suggest that local MnCl2 treatment accelerates fracture healing by increasing mechanical parameters via a potential mechanism of amplified early angiogenesis leading to increased osteogenesis. Therefore, local administration of MnCl2 is a potential therapeutic adjunct for fracture healing.
authors.affiliation: Department of Orthopaedics, Rutgers-New Jersey Medical School, 90 Bergen Street, Suite 7300, Newark, New Jersey, 07103.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hreha
authors.forename: Aaron
authors.initials: A
authors.lastname: Wey
authors.forename: Catherine
authors.initials: C
authors.lastname: Cunningham
authors.forename: Ethan S
authors.initials: ES
authors.lastname: Krell
authors.forename: Eric A
authors.initials: EA
authors.lastname: Brietbart
authors.forename: David N
authors.initials: DN
authors.lastname: Paglia
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Montemurro
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nguyen
authors.forename: Yung-Jae
authors.initials: YJ
authors.lastname: Lee
authors.forename: Daniel
authors.initials: D
authors.lastname: Komlos
authors.forename: Elisha
authors.initials: E
authors.lastname: Lim
authors.forename: Joseph
authors.initials: J
authors.lastname: Benevenia
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Connor
authors.forename: Sheldon S
authors.initials: SS
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002712:Chlorides / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005264:Femoral Fractures / Q000188:drug therapy* / Q000378:metabolism; D017102:Fracture Healing / Q000187:drug effects*; D008297:Male; D017895:Manganese Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000199:Actins; D002712:Chlorides; D017895:Manganese Compounds; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C498862:Acta2 protein, rat; C025340:manganese chloride
keywords: bone regeneration; fracture healing; insulin-mimetic; manganese chloride; rat