The type II collagen fragments Helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation

Abstract

These in vitro and ex vivo experiments of human cartilage suggest that Helix-II and CTX-II could be released in part by different enzymatic pathways. Helix-II and CTX-II alone reflect only partially overall cartilage collagen degradation. These findings may explain why these two biological markers could provide complementary information on disease progression in OA.

Cathepsin L in Normal and Pathological Bone Remodeling

“…In line with this hypothesis, this enzyme has been identified as constituting the major proteolytic activity in osteoclasts, while immunohistochemical studies have specifically localized its presence in intracellular vesicles, in vesicles close to the ruffled border and within the resorption lacunae [6,[8][9][10]. However, growing evidence indicates that, in addition to Cathepsin K, other cysteine proteinases appear to participate in osteoclast-mediated proteolytic degradation of organic bone matrix [6,8,[10][11][12]. In particular, Cathepsin L, a lysosomal endopeptidase mainly involved in tissue degradation and extracellular matrix (ECM) remodeling, appears to make a significant contribution to this process [6,10,12,13].…”

“…Several experimental and clinical investigations indicate that various proteolytic enzymes including matrix metalloproteinases and cysteine proteinases appear to play a major role in the physiological degradation of these macromolecules [6,8,32,49,73]. In particular, Cathepsin L can degrade cartilage-residing proteoglycans, such as aggrecan, and the non-helical telopeptide region of triple helical type I and II collagens [12,60,61,[77][78][79]. The triple helical domain, which is normally resistant to proteolysis, is not degraded by Cathepsin L and requires specific proteases such as Cathepsin K, which cleaves peptide bonds at multiple sites within this domain (Table 1) [9,12,83] It is now well established that the altered activity of these enzymes is responsible for the cartilage destruction and bone erosion associated with most of these diseases [73,[77][78][79][80][81][82].…”

“…In particular, Cathepsin L can degrade cartilage-residing proteoglycans, such as aggrecan, and the non-helical telopeptide region of triple helical type I and II collagens [12,60,61,[77][78][79]. The triple helical domain, which is normally resistant to proteolysis, is not degraded by Cathepsin L and requires specific proteases such as Cathepsin K, which cleaves peptide bonds at multiple sites within this domain (Table 1) [9,12,83] It is now well established that the altered activity of these enzymes is responsible for the cartilage destruction and bone erosion associated with most of these diseases [73,[77][78][79][80][81][82]. In this context, the role of Cathepsin L in pathological bone remodeling is further supported by many experimental observations showing that this proteinase may contribute, in concert with Cathepsin K and MMPs, to facilitating bone resorption by degrading several bone matrix components.…”

“…In addition, Cathepsin L appears to foster bone degradation by acting as mediator of inflammatory processes associated with these diseases [39,[64][65][66][67][68][69]78]. Furthermore, clinical studies highlight that the expression levels of this enzyme are deregulated in several diseases associated with an altered bone turnover such as osteoporosis [15,35,51,67,73,78], rheumatoid arthritis [15,73,[75][76][77][78][79], osteoarthritis [12,15,75,77], loosened joint prosthesis [77], periodontitis [15,64,65], primary bone tumors [81], bone metastasis [81,82] and related malignant hypercalcemia [5,78,81] (Table 2).…”

“…However, growing evidence indicates that, in addition to Cathepsin K, other cysteine proteinases appear to participate in osteoclast-mediated proteolytic degradation of organic bone matrix [6,8,[10][11][12]. In particular, Cathepsin L, a lysosomal endopeptidase mainly involved in tissue degradation and extracellular matrix (ECM) remodeling, appears to make a significant contribution to this process [6,10,12,13].…”