Pit- and trench-forming osteoclasts: a distinction that matters

Osteoclasts (OCs) seeded on bone slices either drill round pits or dig long trenches. Whereas pits correspond to intermittent resorption, trenches correspond to continuous and faster resorption and require a distinct assembly of the resorption apparatus. It is unknown whether the distinction between pits and trenches has any biological relevance. Using OCs prepared from different blood donors, we found that female OCs achieved increased resorption mainly through pit formation, whereas male OCs did so through trench formation. Trench formation went along with high collagenolytic activity and high cathepsin K (CatK) expression, thereby allowing deeper demineralization. A specific CatK inhibitor abrogated the generation of trenches, while still allowing the generation of pits. OCs obtained from bone marrow were more prone to generate trenches than those obtained from blood. Scanning electron microscopy of bone surfaces eroded in vivo showed trenches and pits of similar size as those made by OCs in culture. We conclude that the distinction between trench- and pit-forming OCs is relevant to the differences among OCs from different skeletal sites, different individuals, including gender, and results from differences in collagenolytic power. This indicates a biological relevance and highlights the importance of discriminating between pits and trenches when assessing resorption. Bone resorption: Digging further into bone degradation Danish researchers have shown that the mechanism used by bone-degrading cells (osteoclasts) is determined by their source. Bone degradation by osteoclasts helps growth and repair but, in excess, can cause bone disease. Osteoclasts dig either circular pits or long trenches into bone. Trenches cause faster degradation, but the full significance of the two mechanisms is unknown. Kent Søe and Jean-Marie Delaissé, from the University of Southern Denmark and colleagues examined degradation by osteoclasts from different sources. Osteoclasts generated from bone marrow dug a greater proportion of trenches than osteoclasts generated from blood. Osteoclasts from men dug more trenches than pits, whereas the opposite was true of osteoclasts from women. Inhibiting the enzyme cathepsin K reversed the bias for trenches that was seen with osteoclasts from bone marrow and men, and could lead to a therapy for bone disease.