Page 1 - Gastric pentadecapeptide BPC 157

Journal of
Orthopaedic
Research
ELSEVIER Journal of Orthopaedic Research 21 (2003) 976 -983
www.elsevier.com/locate/orthres

Gastric pentadecapeptide BPC 157 accelerates healing
of transected rat Achilles tendon and in vitro

stimulates tendocytes growth

M. Staresinic, B. Sebecic, L. Patrlj, S. Jadrijevic, S. Suknaic, D. Perovic, G. Aralica,
N. Zarkovic, S. Borovic, M. Srdjak, K. Hajdarevic, M. Kopljar, L. Batelja,
A. Boban-Blagaic, 1. Turcic, T. Anic, S. Seiwerth, P. Sikiric *

Abstract

In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157
(GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-I 16, PL 14736, Pliva), it
ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal
insertion) presents with a large tendon defect between cut ends. Agents (ikg b.w., i.p., once time daily) (BPC 157 (dissolved in saline,
with no carrier addition) ( 10 pg. 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at
24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopicdl
assessment was on day 1. 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide
BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of Failure per area and Young's modulus of
elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior
formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the
reestablishment of full tendon integrity. Likewise, unlike TGF-P, pentadecapeptide BPC 157, presenting with no effect on the growth
of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is
opposed in both combinations: BPC 157 + HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured
tendocytes) and HNE + BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived
conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable
delivery, usefully favor gastric pentadecapeptide BPC 157 in future Achilles tendon therapy.
0 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Kcj.ii.or.tO; Achilles tendon transection; Gastric pentadecapeptide BPC I57 functional: Biomechanical; Microscopical and clinical recovery; Rats;
Growth of cultured rat tendocytes

Introduction IGF-I variant form of IGF-I) [ 101 or collagen sponges in
the tendon defects (growth and differentiation factors
Most protein growth factors that might improve the (GDFs) 5,6,7) [l] were suggested. However, all special
healing following tendon rupture are rapidly metabo- regimens reflect uncertain and limited delivery regularly
lized by the organism [l]. To benefit from an otherwise inappropriate for routine use. To this end, our focus is a
weak activity of peptides, parallel with attempts to fur- stable gastric pentadecapeptide BPC 157, currently in
ther improvement of the peptides carriers [25] needed for clinical trials for inflammatory bowel disease (PL-10,
peptidergic agents activity, an injection close to the site PLD-I 16, PL 14736, Pliva).
of the wound (urogastrone (epidermal growth factor Transected rat Achilles tendon likely recovery begins
(EGF)) [7], or into the wound (the recombinant LR3- with pentadecapeptide BPC 157 active given systerni-
cally and/or locally [X, 12,16,17,19%21,3 11, and its healing
effects on various tissues [X, I 2,16,17,19-2 l,3 I]. Initially,
*Corresponding author. Tel.: +385-1-4566-833/834: fax: +385-1-
492-00-50. as a gastric pentadecapeptide, BPC 157 opposes a va-
E-IIILI~~ trtltlrcw: sikiric(u;inef.hr (P. Sikiric). riety of gastrointestinal lesions (i.e., 112,191). Later, it
0736-02661s - see front matter 0 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved
doi: 1O.lO16/S0736-0266(03)00l10-4