Effect of Collagen Oligopeptide Injection on Rabbit Tenositis

Abstract

ABSTRACT. Effects of the collagen oligopeptide (COP) were examined by its repeat injection into the inflammatory rabbit Achilles tendon (Tendo calcaneus communis), in which tenositis was induced by injection of bacterial collagenase. COP was evaluated 5 times over a period of 3 weeks to 1 month after injection of collagenase. At 1 month after treatment, the therapeutic effect of COP was evaluated by examining the structure of collagen fibrils, amount and components of glycosaminoglycans (GAGs) and matrix metalloproteinases (MMPs), and compared with the saline injection, control, and normal groups. The Achilles tendon of rabbit in the control group (no COP injection) and saline injection group showed a notable increase in the number of fine collagen fibrils, a change in GAG composition and increase in the amount of pro-MMP-2, indicating the weakening of the tendon. In contrast, the size distribution of collagen fibrils, GAG composition and the amount of pro-MMP-2 was similar to those in the normal group. These results suggest that COP injection promotes healing processes of the tendon injury. KEY WORDS: collagen fibril, collagen oligopeptide, electron microscopy, glycosaminoglycans, rabbit tendon.J. Vet. Med. Sci. 70(12): 1295-1300, 2008 The basic function of a tendon is to convey the force exerted by a muscle to the bone. The mechanical load is not transmitted directly to the bone because tendon is a highly flexible connective tissue. This connective tissue is composed of two components: tendon cells and extracellular matrix (ECM) that consists of collagen and proteoglycans [1,21]. Collagen in a tendon is composed of mainly type I collagen and is arranged into bundles of collagen fibrils that are further organized into tendon fascicles [22]. Proteoglycan has its core protein covalently bound to glycosaminoglycan (GAG). GAG is a non-branched polysaccharide consisting of repeated units of amino acids and uronic acids. GAGs in ECM exist as proteoglycans except for hyaluronic acid (HA) that exists as a free GAG. Proteoglycans are classified into chondroitin sulphate (CS), dermatan sulphate (DS), heparan sulphate (HS), heparin or keratan sulphate according to their uronic acid subunit [3]. Decorin is the most abundant DS proteoglycan in tendon, and is reportedly involved in both the formation of collagen fibrils and adjustment of collagen fibril diameter [37]. However, its role in the turnover of tendon ECM has not yet been elucidated [16].Matrix metalloproteinase (MMP) is an enzyme that has zinc ion in its active core and requires calcium ion for maintenance of the activity. More than 20 types of MMP have been reported so far, and they play an important role in the turnover of tendon ECM [7,34]. MMPs are divided into the following types: collagenase (MMP-1, -8, -13), gelatinase (MMP-2, -9), stromelysin (MMP-3, -10), membrane , and others (including MMP-7, -11, -12) according to their biochemical properties [4]. However, how these MMPs are involved in the turnover of tendon ECM remains unclear.Inflammation of a tendo...

The past, present and future in scaffold-based tendon treatments

“…Clinically, injectable collagen hydrogels have been utilised as carriers for biological and pharmaceutical agents [128]. Collagen peptides have also been used, with preclinical data demonstrating increased collagen synthesis [129], maintenance of homeostasis [130] and improved healing, as judged by mean average diameter, distribution of fibrils and GAG composition [131]. The utilisation of fibrin has been advocated based on its high cytocompatibility, biodegradability, controllable cross-linking, carrier capacity and presence of several ECM proteins, such as fibronectin, that enhance cell adhesion and proliferation [132][133][134].…”

Efeito do laser de baixa potência (810 nM) na tendinite induzida por colagenase em tendão calcâneo de ratos.

“…Consequentemente é necessário desenvolver novos métodos terapêuticos eficazes que evitem o processo degenerativo da matriz extracelular e o desenvolvimento de uma regeneração rápida sem formação de cicatriz, que alteraria bastante as propriedades mecânicas do tendão (UEDA et al, 2008).…”

“…As MMPs são enzimas de ação proteolítica e possuem um importante papel na modulação da matriz extracelular do tendão, entretanto o mecanismo desta modulação ainda permanece obscuro (UEDA et al, 2008). Estas enzimas foram caracterizadas inicialmente como proteases de degradação, pela capacidade de degradar os componentes da matriz extracelular, influenciando em processos importantes como a proliferação, diferenciação, migração e morte celular, assim como a interação entre células, quimiocinas, citocinas e fatores de crescimento, apresentando um papel crucial em muitos processos fisiológicos e em muitas condições patológicas (MCCAWLEY et al, 2001;VANLINT et al, 2007).…”

“…MMPs de membrana 15,16,17, 24 e 25) e outras que são classificadas de acordo com suas propriedades bioquímicas (UEDA et al, 2008). O aumento da expressão de MMP foi observada em várias doenças, no ser humano e em outros animais, onde a inflamação está presente, sugerindo que as MMPs possam proteger ou contribuir para a patologia, possuindo papel modulador no processo inflamatório (PARKS et al, 2004;MANICONE et al, 2008).…”

“…Desta forma, a supressão de algumas MMPs poderia auxiliar no reparo do tendão (UEDA et al, 2008). Tanto no ser humano como em outros animais com tendinopatias, a MMP-13 poderia apresentar uma ação comparável a MMP-1, e seu aumento poderia significar uma maior degradação da matriz extracelular (SUN et al, 2008).…”