Osteoarthritis: Current Molecular Biomarkers and the Way Forward
The ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeost…
Journal:
Authors:
- Kraus VB,
- Karsdal MA,
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy
Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We …
Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Löfvall H,
- Kertész Z,
- Montano C,
- Bjurström CF,
- Karsdal MA,
- Schulz AS,
- Richter J,
- Henriksen K,
A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation
Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating that…
Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Flores C,
- Thomsen JS,
- Brüel A,
- Gudmann NS,
- Hauge EM,
- Karsdal MA,
- Richter J,
- Henriksen K,
Osteoclast-derived coupling factors in bone remodeling
In the bone remodeling process that takes place throughout the skeleton at bone multicellular units, intercellular communication processes are crucial. The osteoblast lineage has long been known to program osteoclast formation and hence resorption, but the preservation of bone mass and integrity req…
Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Martin TJ,
Imatinib mesylate does not increase bone volume in vivo
Imatinib mesylate is a tyrosine kinase inhibitor used in the management of disorders in which activation of c-Abl, PDGFR, or c-Kit signaling plays a critical role. In vitro, imatinib stimulates osteoblast differentiation, inhibits osteoblast proliferation and survival, and decreases osteoclast devel…
Journal:
Authors:
- O'Sullivan S,
- Naot D,
- Callon KE,
- Watson M,
- Gamble GD,
- Ladefoged M,
- Karsdal MA,
- Browett P,
- Cornish J,
- Grey A,
Ion transporters involved in acidification of the resorption lacuna in osteoclasts
Osteoclasts possess a large amount of ion transporters, which participate in bone resorption; of these, the vacuolar-adenosine trisphosphatase (V-ATPase) and the chloride-proton antiporter ClC-7 acidify the resorption lacuna. However, whether other ion transporters participate in this process is cur…
Journal:
Authors:
- Henriksen K,
- Sørensen MG,
- Jensen VK,
- Dziegiel MH,
- Nosjean O,
- Karsdal MA,
Characterization of the bone phenotype in ClC-7-deficient mice
Mice deficient in the chloride channel ClC-7, which is likely involved in acidification of the resorption lacuna, display severe osteopetrosis. To fully characterize the osteopetrotic phenotype, the phenotypes of osteoclasts and osteoblasts were evaluated. ClC-7(-/-) mice and their corresponding wil…
Journal:
Authors:
- Neutzsky-Wulff AV,
- Karsdal MA,
- Henriksen K,