Effect of GDF‐5 on ligament healing

Abstract

The effects of growth and differentiation factor-5 (GDF-5) on ligament healing were studied using a gap injury model of the medial collateral ligament in rat knee joints. The administration of GDF-5 once at the time of surgery significantly improved the mechanical properties of the femur-ligament-tibia complex. At 3 weeks after surgery, 30 mg of GDF-5 improved the ultimate tensile strength of the complex by 41%, and the stiffness by 60%, compared with the vehicle control ( p < 0.05 for both; Fisher's PLSD test). The observation with a transmission electron microscopy revealed that GDF-5 increased the diameter of collagen fibrils in the repair tissue, which was considered to be a possible mechanism for the positive result in the biomechanical testing. Quantitative PCR and in situ hybridization revealed enhanced type I procollagen expression by GDF-5, and the PCR analysis also revealed that the GDF-5 treatment reduced the expression of type III procollagen relative to type I procollagen. The PCR analysis further showed that the expression of decorin and fibromodulin was relatively reduced against type I procollagen by the growth factor, which was considered to be responsible for the increase of collagen fibril diameter in the repair tissue. No adverse effects were observed, and the use of GDF-5 was considered a promising approach to facilitate ligament healing. ß

Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat

“…In conclusion, the BPC 157 ligament healing may be clinically relevant (i.e., no knee joint contracture, no obvious valgus instability, preserved muscle motor function and walking pattern), thus, the significant knee joint failure counteracted (as important proof of the activity that is lacking in the standard peptide studies 3,14,16,17,18 ).…”

“…Function in either condition, normal (walking rats) and stressed (running rats), biomechanic, macro/microscopy were noted superior as before [1][2][3][4][5][6][7][8][9][10][11][12] in tendon studies 1,2,10 and other wound studies, 4,9,10,12 , not species related. This may be a wound healing (not found with standard peptide factors 3,16,17 ) more apt to predispose the ligament to improved healing course after transection. Anyway, such parallelism (but, no overlap) in the BPC 157 healing of ligament or tendon, after transection or detachment and in bone-healing, 1-12 is complementary to improvement (biomechanical, functional, microscopic/immunochemical, macroscopic) with multiple modes of therapy regimens and the ligaments providing structural support around joint capsules and at sites where bones make contact with other bones.…”

The Effects of GDF-5 and Uniaxial Strain on Mesenchymal Stem Cells in 3-D Culture

“…More notably, decreased collagen content and tensile strength [37], as well as delayed healing, have been reported in the Achilles tendon of GDF-deficient mice [13]. Conversely, exogenous GDF protein delivered by carrier [3,46], suture coating [43], or adenoviral transfection [44] improves tendon healing and tensile strength of transected tendons.…”

Nerve growth factor improves ligament healing

“…1,6,7 Individual growth factors have different effects on different cells during the healing process, and certain growth factors regulate the expression of other growth factors through both autocrine and paracrine feedback loops. 1,6 Several studies have demonstrated beneficial effects of selected growth factors on aspects of ligament healing, including platelet-derived growth factor (PDGF), 8,9 insulin-like growth factor (IGF), 8 transforming growth factor beta-1 and 2 (TGF-b1 and 2), 9,10 and growth and differentiation factor-5 (GDF-5), 11 when used alone or in multiple application. Nevertheless, it remains unclear what factors play the key roles in promoting ligament healing, which growth factor has the maximum effect, or what combinations might create synergistic effects.…”