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

Abstract

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.

Tendon Healing with Growth Factors

“…In our one studies we observe a high concentration of TGF-β initially, which then decreased for 2 and 4 weeks and then increase massively at 8 weeks, possibly reflecting the initial inflammation and activation of cells, followed by an intermediary period and then the remodeling of the tendon with increased apoptosis of no longer necessary cells. The results are similar to those for the rat rotatory cuff (Würgler-Hauri et al, 2007), although we observe a steeper increase at 8 weeks.…”

“…Our results thus suggest a tightly controlled BMP-12 concentration, which possibly helps to coordinate the newly produced cells during proliferation in the early healing period. This is also seen with the rat rotatory cuff (Würgler-Hauri et al, 2007), yet we do not see an increase in concentrations after 8 weeks, again possibly reflecting the difference in both tendons.…”

Mechanical Load and BMP Signaling During Tendon Repair: A Role for Follistatin?

“…GDF-5 and -6 have been detected in human tendon by immunohistochemistry, especially in metabolically active cells [8,18]. During tendon to bone healing in rats, immunohistochemistry demonstrates increased expression of GDF-5, -6, and -7 [19]. Healing of the rat Achilles tendon is sensitive to mechanical loading.…”

Strategies in Biologic Augmentation of Rotator Cuff Repair: A Review

“…Bone morphogenic protein (BMP) 12 to 14, expressed in active fibroblasts and heavily involved in de novo joint formation, were present throughout the healing process of the boneto-tendon insertion [49,57]. Seeherman et al [49] demonstrated in a full-thickness rotator cuff tear sheep model that delivery of rhBMP-12 in sponge carriers had the potential to accelerate healing of rotator cuff repairs when compared to untreated controls.…”