Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification
Osteoclasts degrade bone matrix by secretion of hydrochloric acid and proteases. We studied the processes involved in the degradation of the organic matrix of bone in detail and found that lysosomal acidification is involved in this process and that MMPs are capable of degrading the organic matrix i…
Journal:
Authors:
- Henriksen K,
- Sørensen MG,
- Nielsen RH,
- Gram J,
- Schaller S,
- Dziegiel MH,
- Everts V,
- Bollerslev J,
- Karsdal MA,
Diphyllin, a novel and naturally potent V-ATPase inhibitor, abrogates acidification of the osteoclastic resorption lacunae and bone resorption
Dissolution of the inorganic phase of bone by the osteoclasts mediated by V-ATPase and ClC-7 is a prerequisite for bone resorption. Inhibitors of osteoclastic V-ATPase or ClC-7 are novel approaches for inhibition of osteoclastic bone resorption. By testing natural compounds in acidification assays, …
Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Neutzsky-Wulff AV,
- Dziegiel MH,
- Karsdal MA,
Are nonresorbing osteoclasts sources of bone anabolic activity?
Some osteopetrotic mutations lead to low resorption, increased numbers of osteoclasts, and increased bone formation, whereas other osteopetrotic mutations lead to low resorption, low numbers of osteoclasts, and decreased bone formation. Elaborating on these findings, we discuss the possibility that …
Journal:
Authors:
- Karsdal MA,
- Martin TJ,
- Bollerslev J,
- Christiansen C,
- Henriksen K,
The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation
Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone formati…
Journal:
Authors:
- Schaller S,
- Henriksen K,
- Sveigaard C,
- Heegaard AM,
- Hélix N,
- Stahlhut M,
- Ovejero MC,
- Johansen JV,
- Solberg H,
- Andersen TL,
- Hougaard D,
- Berryman M,
- Shiødt CB,
- Sørensen BH,
- Lichtenberg J,
- Christophersen P,
- Foged NT,
- Delaissé JM,
- Engsig MT,,
- Karsdal MA,
The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation
Bone resorption may generate collagen fragments such as ICTP and CTX, which can be quantified in serum and/or urine by using specific immunoassays, and which are used as clinical markers. However, the relative abundance of ICTP and CTX varies according to the type of bone pathology, suggesting that …
Journal:
Authors:
- Garnero P,
- Ferreras M,
- Karsdal MA,
- Nicamhlaoibh R,
- Risteli J,
- Borel O,
- Qvist P,
- Delmas PD,
- Foged NT,
- Delaissé JM,