Temporal expression of 8 growth factors in tendon-to-bone healing in a rat supraspinatus model.

Growth factors play an important role in supraspinatus tendon-to-bone healing. The objective of this study was to evaluate the temporal expression of 8 different growth factors in tendon-to-bone healing in an animal model. We hypothesize that growth factors exhibit unique temporal profiles that correlate to specific stages in the acute process of the supraspinatus tendon. To test this hypothesis, rats underwent bilateral supraspinatus tendon detachment and repair. Animals were euthanized at 1, 2, 4, 8, and 16 weeks. Immunohistochemical staining was done using antibodies for basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12), BMP-13, BMP-14, cartilage oligomeric matrix protein (COMP), connective tissue growth factor (CTGF), platelet-derived growth factor-B (PDGF-B), and transforming growth factor-beta1 (TGF-beta1). Immunoassays showed an increase in the expression of all growth factors at 1 week, followed by a return to control or undetectable levels by 16 weeks in both the insertion and midsubstance. Future studies will investigate the different impacts of growth factor expression in tendon to bone healing.

Fibrinogen Philadelphia, a hypodysfibrinogenemia characterized by abnormal polymerization and fibrinogen hypercatabolism due to gamma S378P mutation.

Fibrinogen Philadelphia, a hypodysfibrinogenemia described in a family with a history of bleeding, is characterized by prolonged thrombin time, abnormal fibrin polymerization, and increased catabolism of the abnormal fibrinogen. Turbidity studies of polymerization of purified fibrinogen under different ionic conditions reveal a reduced lag period and lower final turbidity, indicating more rapid initial polymerization and impaired lateral aggregation. Consistent with this, scanning and transmission electron microscopy show fibers with substantially lower average fiber diameters. DNA sequence analysis of the fibrinogen genes A, B, and G revealed a T>C transition in exon 9 resulting in a serine-to-proline substitution near the gamma chain C-terminus (S378P). The S378P mutation is associated with fibrinogen Philadelphia in this kindred and was not found in 10 controls. This region of the gamma chain is involved in fibrin polymerization, supporting this as the polymerization defect causing the mutation. Thus, this abnormal fibrinogen is characterized by 2 unique features: (1) abnormal polymerization probably due to a major defect in lateral aggregation and (2) hypercatabolism of the mutant protein. The location, nature, and unusual characteristics of this mutation may add to our understanding of fibrinogen protein interactions necessary for normal catabolism and fibrin formation.