Collagenase-3 (MMP-13) is expressed by hypertrophic chondrocytes, periosteal cells, and osteoblasts during human fetal bone development

Abstract

Collagenase‐3 (MMP‐13) is a novel matrix metalloproteinase, the expression of which has so far only been documented in human breast carcinomas and osteoarthritic cartilage. In this study we have examined the expression of MMP‐13 during human fetal development. Northern blot hybridizations revealed abundant expression of MMP‐13 mRNAs in total RNA from fetal cartilage and calvaria at gestational age of 15 weeks. By in situ hybridization MMP‐13 transcripts were detected in chondrocytes of hypertrophic cartilage in vertebrae of the spinal column and in the dorsal end of ribs undergoing ossification, as well as in osteoblasts and periosteal cells below the inner periosteal region of ossified ribs. In contrast, no expression of MMP‐13 could be detected in osteoclasts. Furthermore, expression of MMP‐13 mRNA was detected in osteoblasts and fibroblasts primarily on the inner side of calvarial bone of the skull at 16 weeks of gestation. Expression of MMP‐13 mRNA by primary human fetal chondrocytes in culture was enhanced by transforming growth factor‐β (TGF‐β) and inhibited by bone morphogenetic protein‐2 (BMP‐2). No expression of MMP‐13 mRNA could be noted in other fetal tissues, including the skin, lungs, neural tissue, muscle, and liver. These results suggest that MMP‐13 plays an important role in the extracellular matrix remodeling during fetal bone development both via endochondral and intramembranous ossification. Dev. Dyn. 208:387–395, 1997. © 1997 Wiley‐Liss, Inc.

Matrix remodeling during endochondral ossification

“…At the chondroosseous junction, MMP13 is expressed by the newly recruited osteoblasts adjacent to tartrateresistant acid phosphatase (TRAP)-positive cells [25]. Particular intramembranous bones of the human fetus show the same expression pattern, with a strong expression first observed at 10 weeks of gestation [26] in osteoblasts lining the inner side of the calvaria [27]. At the secondary sites of ossification, MMP13 is expressed at the blind end of excavated canals formed by osteoclasts and along the walls of the forming-marrow space [28].…”

Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells

“…Collagenases are the principal proteinases capable of cleaving native fibrillar collagens (Ala-aho and Ka¨ha¨ri, 2005). Collagenase-3 (MMP-13) has a notably wide substrate specificity, and its expression is limited to physiologic situations, in which rapid and effective remodeling of collagenous ECM is required, for example fetal development of bone, postnatal bone remodeling, and gingival and fetal skin wound repair (Johansson et al, 1997b;Sta˚hle-Ba¨ckdahl et al, 1997;Ravanti et al, 1999Ravanti et al, , 2001). However, the wide substrate specifity of MMP-13 suggests that it is also a powerful invasion tool for cancer cells.…”

Targeted inhibition of human collagenase-3 (MMP-13) expression inhibits squamous cell carcinoma growth in vivo

“…Collagenase-1 (MMP-1), collagenase-2 (MMP-8), and collagenase-3 (MMP-13) are the principal neutral proteinases responsible for cleavage of native fibrillar collagens of type I, II, III, and V. MMP-13 also cleaves several other ECM components, including type IV, X, and XIV collagens, large tenascin C, fibronectin, aggrecan, versican, and fibrillin-1 (Fosang et al, 1996;Kna¨uper et al, 1996;Ashworth et al, 1999), as well as non-ECM components, such as chemokines macrophage chemotactic protein-3 and stromal cell-derived factor-1 (McQuibban et al, 2000(McQuibban et al, , 2001. The physiologic expression of MMP-13 is limited to situations in which rapid remodeling of collagenous ECM is required, for example, fetal bone development (Johansson et al, 1997b) and fetal skin and adult gingival wound repair (Ravanti et al, 1999b;. The expression of MMP-13 has also been detected in invasive neoplastic tumors, that is, breast carcinomas (Freije et al, 1994), squamous cell carcinomas (SCCs) of the head and neck (Airola et al, 1997;Johansson et al, 1997a;Cazorla et al, 1998), vulva (Johansson et al, 1999), and esophagus (Etoh et al, 2000), in chondrosarcomas (Urı´a et al, 1998), primary and metastatic melanomas (Airola et al, 1999;Nikkola et al, 2001), and urothelial carcinomas (Bostro¨m et al, 2000).…”