Potential Therapeutic Use of Relaxin in Healing Cranial Bone Defects
Abstract
The overall objective is to provide proof-of-principle that recombinant human relaxin (rhRLX) administration will accelerate bone healing in a calvarial defect model in mice by promoting angiogenesis/vasculogenesis and osteogenesis, at least in part through incorporation of bone marrow-derived angio- and osteogenic progenitor cells into the lesion. Results from the initial study conducted during this reporting period demonstrated: successful production of chimeric mice after irradiation and GFP+ bone marrow transplantation; reproducible implementation of uniform cranial lesions of ~1.5 mm diameter, and circulating concentrations of relaxin ranging from 30-80 ng/ml. However, after 11 weeks of healing, the lesion closure was comparable in the relaxin- and vehicle-treated mice (~70%). Therefore, in the next study we will decrease the healing time to 4 and 8 weeks in order to assess whether the closure occurs more rapidly with relaxin treatment. In view of the biphasic dose response curve for relaxin, which is dependent on the functional endpoint, we will also reduce the infusion rate by 20-fold to 0.05 microgram/h, which in our experience should produce a circulating relaxin concentration of 1-5 ng/ml.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2016
- Accession Number
- AD1033889
Entities
People
- Kirk P Conrad
Organizations
- University of Florida