They display a characteristic ruffled border where proteases and acid are secreted, allowing for bone resorption and formation of ‘resorption pits’ in the bone surface [25]. Osteoclast morphology varies between mammals and teleosts (bony fishes), and also between different groups of teleosts [20]. In the skeleton of young zebrafish for example, osteoclast activity is carried out by both mononucleated and multinucleated cells [26]. In fact, there is an ontogenetic progression from mono- towards multinucleated osteoclasts. In juvenile zebrafish, bone resorbing cells in the developing lower jaw are

at first mononucleated. In thin skeletal tissues such as the neural arch, mononucleated cells are even predominant in adults [26]. In rainbow trout, scale resorption Selleckchem CT99021 selleck chemicals llc is predominantly carried out by mononucleated osteoclasts [27]. Although in mammals these mononucleated cells are often just regarded as osteoclast precursors, in fish mononucleated osteoclasts are active bone resorbing cells [28] and [29]. One family of osteoclast proteases

is the matrix metalloproteinases (MMPs). They are involved in the breakdown of extracellular matrix by osteoclasts, but also by other cell types like fibroblasts [30]. MMPs are multi-domain enzymes that require zinc as cofactor for proteolytic activity. Extracellular matrix turnover occurs in a wide range of physiological processes, including embryonic development and morphogenesis, bone resorption and tissue regeneration. Moreover, MMP-mediated breakdown of the extracellular matrix has been implicated in disease processes including cartilage destruction in osteoarthritis [31]. The importance of MMPs in bone development is underlined by studies on mmp2 and mmp9 null mice, which suffer from bone abnormalities, osteoporosis and osteopetrosis respectively [32]. In view of their role in physiological and pathological see more processes, MMPs are important targets in pharmaceutical research and drug development. In bone turnover, secreted MMPs participate in the breakdown of collagen, which in turn allows osteoclast attachment [33]. Furthermore, MMP-9 is associated with osteoclast migration through the collagen

matrix [34]. Matrix metalloproteinases may also break down residual collagen left by cathepsin K after the pH rises in the resorption pit [35]. MMP-2 and MMP-9 (gelatinases A and B, respectively) are particularly active against gelatins (denatured collagens) and intact collagen types I and IV. In bone of dermal origin, matrix degradation is thought to rely more on MMPs and less on cathepsin K [36]. MMP-2 has also been described to play a crucial role in formation and maintenance of the osteocytic canalicular network, whereas MMP-9 is active in early calvarian bone development and in orthodontic tooth movement [37], [38] and [39]. Regenerating fins of adult zebrafish expresses mmp-2 and regeneration can be inhibited by the MMP inhibitor GM6001 [40].