Does BMP2 play a role in the pathogenesis of equine degenerative suspensory ligament desmitis?

Abstract

Objective: Horses afflicted with degenerative suspensory ligament desmitis (DSLD) suffer from progressive leg pain and lameness without history of trauma. DSLD is a systemic disorder caused by abnormal accumulation of proteoglycans in many connective tissues. One proteoglycan found in higher quantities in DSLD is decorin. The accumulated decorin has an abnormally glycosylated glycosaminoglycan chain in DSLD. In addition to acellular accumulations of proteoglycans foci of active fibroblasts/tenoblasts were observed in some tendons and suspensory ligaments (SLs) from DSLD cases We have hypothesized that this represents an early event in DSLD and that production of chondrogenic growth factors, such as BMP2, and/or enzyme participating in glycosylation of glycosaminoglycans is a major factor in initiation and progression of DSLD.

Results: Using immunohistochemistry we have identified BMP2 in these cellular foci, indicating association with proteoglycan production, but not in other cells in the tendon and SLs. In contrast, very little staining for TGFβ and dermatan sulfate epimerase, an enzyme involved in glycosylation of glycosaminoglycan chains, was observed in these foci and other cells in both control and DSLD-affected tendons and SLs. Our data support our hypothesis that chondrogenic growth factors may be responsible, at least in part for progression of DSLD in horses.

Keywords: BMP2; Equine degenerative suspensory ligament desmitis; Proteoglycans.

Fig. 1

Basic histopathology of DSLD lesions. a Histology of normal tendon shows bundles and fascicles separated by septa of less organized and somewhat loose connective tissue that contains fibroblasts, loose collagen fibers, adipose tissue and small blood vessels (↓). b A DSLD-affected tendon shows infiltration of proteoglycans (staining dark blue or purple) obscuring the normal architecture of the tendon. c Cellular lesions are visualized as distinct foci consisting of spindly active fibroblasts/tenoblasts, arranged in whorls. The presence of small amounts proteoglycans is limited to the cytoplasm of these cells. d Reveals an area of septum with increased number of fibroblasts containing small amount of proteoglycans (↓). Numerous small blood vessels are present as well (*). All four sections are stained with hematoxylin and eosin

Fig. 2

Immunohistochemical visualization of TGFβ-1 and BMP2. Using immunohistochemistry only little TGFβ-1was visualized in fibroblasts and tenoblasts, in both control (a) and DSLD-affected (b) tendons. c Reveals hematoxylin and eosin stained cellular foci and whorls in DSLD-affected tendons. d The cells in these foci immunostained strongly for BMP2. No or only little BMP2 was present in acellular areas or masses containing proteoglycans (e) and likewise no or very little BMP2 was identified in cells of the control tendons (f)