Publications
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Background: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. Methods: IMO iPSCs were generated from a patient carrying a homozygous ...
May 15, 2020
Journal:
Stem Cells Res Ther
Author:
Xian X, Moraghebi R, Löfvall H, Fasth A, Henriksen K, Richter J, Woods NB, Moscatelli I
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th...
Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by nonfunctional osteoclasts. Approximately 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. Gene therapy represents a potential alternative treatment ...
June 10, 2019
Journal:
Hum Gene Ther
Author:
Löfvall H, Rothe M, Schambach A, Henriksen K, Richter J, Moscatelli I
Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast p...
January 12, 2019
Journal:
Hum Genet.
Author:
Segovia-Silvestre T, Neutzsky-Wulff AV, Sorensen MG, Christiansen C, Bollerslev J, Karsdal MA, Henriksen K
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically...
July 20, 2017
Journal:
Hum Gene Ther
Author:
Moscatelli I, Löfvall H, Rothe M, Montano C, Kertész Z, Sirin M, Schulz AS, Schambach A, Henriksen K, Richter J, Thudium CS
Objectives: Here, we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in cord blood (CB) CD34+ cells would induce differentiation and survival of monocytes and osteoclasts in vitro and in vivo. Methods: Human M-CSF was overexpressed in cord blood CD34+ cells using a lentiviral vector. ...
February 3, 2017
Journal:
Eur J Hematology
Author:
Montano Almendras CP, Thudium CS, Löfvall H, Moscatelli I, Schambach A, Henriksen K, Richter J
IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in po...
August 16, 2016
Journal:
JAMA.
Author:
Miller PD, Hattersley G, Riis BJ, Williams GC, Russo LA, Alexandersen P, Zerbini CA, Hu MY, Harris AG, Fitzpatrick LA, Cosman F, Christiansen C, Lau EM
In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery ...
Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, re...
January 6, 2016
Journal:
Nat Commun.
Author:
Styrkarsdottir U, Thorleifsson G, Gudjonsson SA, Sigurdsson A, Center JR, Lee SH, Nguyen TV, Kwok TC, Lee JS, Ho SC, Woo J, Leung PC, Kim BJ, Rafnar T, Kiemeney LA, Ingvarsson T, Koh JM, Tang NL, Eisman JA, Christiansen C, Sigurdsson G, Thorsteinsdottir U, Stefansson K
Estrogen and bone health form a cornerstone of osteoporosis management. Diagnosis of osteoporosis is performed using bone mineral density (BMD), despite the limitations associated with this. Within the last 25 years, numerous bone turnover markers (BTM) have been developed, and this has led to a mar...
ClC-7, located in late endosomes and lysosomes, is critical for the function of osteoclasts. Secretion of Cl(-) by the ruffled border of osteoclasts enables H(+) secretion by v-H(+)-ATPases to dissolve bone mineral. Mice lacking ClC-7 show altered lysosomal function that leads to severe lysosomal st...
September 8, 2015
Journal:
Cell Tissue Res.
Author:
Guo J, Bervoets TJ, Henriksen K, Everts V, Bronckers AL
Abstract Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation w...
July 1, 2015
Journal:
J Exp Biol
Author:
McGee-Lawrence M, Buckendahl P, Carpenter C, Henriksen K, Vaughan M, Donahue S
Introduction: Osteoporosis is a major health care problem, and whereas efficacious treatments for vertebral fracture reduction are available for osteoporosis patients, these therapies are still limited with respect to capacity for restoration of bone loss, as well as efficacy on non-vertebral fractu...
May 10, 2015
Journal:
Expert Opin Ther Targets
Author:
Henriksen K, Thudium CS, Christiansen C, Karsdal MA
Objective: Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporos...
October 6, 2013
Journal:
Clin Biochem
Author:
Sun S, Karsdal MA, Bay-Jensen AC, Sørensen MG, Zheng Q, Dziegiel MH, Maksymowych WP, Henriksen K
The unique ability of the osteoclasts to resorb the calcified bone matrix is dependent on secretion of hydrochloric acid. This process is mediated by a vacuolar H+ ATPase (V-ATPase) and a chloride-proton antiporter. The structural subunit of the V-ATPase, a3, is highly specific for osteoclasts, and ...
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...
October 1, 2011
Journal:
Calcif Tissue Int.
Author:
O'Sullivan S, Naot D, Callon KE, Watson M, Gamble GD, Ladefoged M, Karsdal MA, Browett P, Cornish J, Grey A
Summary: Early prognosis of osteoporosis risk is not only important to individual patients but is also a key factor when screening for osteoporosis drug trial populations. We present an osteoporosis fracture risk score based on vertebral heights. The score separated individuals who sustained fractur...
July 22, 2011
Journal:
Osteoporos Int.
Author:
Lillholm M, Ghosh A, Pettersen PC, de Bruijne M, Dam EB, Karsdal MA, Christiansen C, Genant HK, Nielsen M
Objective: The objective of this post hoc analysis was to investigate the effect of strontium ranelate on a cartilage degradation marker in postmenopausal women who participated in a randomized, placebo-controlled osteoporosis study. Women were stratified according to reported symptoms of osteoarthr...
The osteoclast initiates resorption by creating a resorption lacuna. The ruffled border surrounding the lacunae arises from exocytosis of lysosomes. To dissolve the inorganic phase of the bone, the vacuolar adenosine triphosphatase, located in the ruffled border, pumps protons into the resorption la...
April 11, 2010
Journal:
Assay Drug Dev Technol
Author:
Jensen VK, Nosjean O, Dziegiel MH, Boutin JA, Sørensen MG, Karsdal MA, Henriksen K
Background: Bone size (BS) variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the PLCL1 (phospholipase c-like 1) locus. Carriers o...
December 23, 2009
Journal:
BMC Med Genet.
Author:
Cauchi S, Byrjalsen I, Durand E, Karsdal MA, Froguel P
Aims: To investigate the influence of food intake on the bioavailability and pharmacodynamic effects of salmon calcitonin (sCT). Methods: A single-blind, randomized, partly placebo-controlled study was conducted in 36 healthy postmenopausal female volunteers aged 62-74 years. The influence of food ...
April 4, 2009
Journal:
Br J Clin Pharmacol
Author:
Karsdal MA, Byrjalsen I, Azria M, Arnold M, Choi L, Riis BJ, Christiansen C
Anti-resorptive strategies may affect bone collagen maturation differently depending on the mode of action. Orally administrated calcitonin resulted in a dose dependent inhibition of bone resorption but did not change bone collagen maturation. This may reflect aspects of bone quality. INTRODUCTION:...
September 19, 2008
Journal:
Osteoporos Int.
Author:
Karsdal MA, Byrjalsen I, Leeming DJ, Delmas PD, Christiansen C
Background: To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT). Methods: The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I stud...
Postmenopausal osteoporosis results from a continuous imbalance between bone resorption and bone formation, favoring bone resorption. An increasing number of treatments for osteoporosis are in development and on the market. A range of differences and similarities are found between these treatment op...
Bone turnover is a highly regulated process, where bone resorption in the normal healthy individual always is followed by bone formation in a manner referred to as coupling. Patients with osteopetrosis caused by defective acidification of the resorption lacuna have severely decreased resorption, in ...
February 8, 2008
Journal:
Biochem Biophys Res Commun.
Author:
Neutzsky-Wulff AV, Dziegiel MH, Christiansen C, Henriksen K, Karsdal MA
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, ...
October 22, 2007
Journal:
J Bone Miner Res
Author:
Sørensen MG, Henriksen K, Neutzsky-Wulff AV, Dziegiel MH, Karsdal MA
We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of age...
June 18, 2007
Journal:
Osteoporos Int.
Author:
Henriksen K, Leeming DJ, Byrjalsen I, Nielsen RH, Sorensen MG, Dziegiel MH, Martin TJ, Christiansen C, Karsdal MA
Numerous experimental and clinical observations suggest that overall changes in bone resorption during menopause or treatment with hormone replacement therapy (HRT) are combined effects of changes in osteoclast number and function. Moreover, due to a coupling between osteoclastic bone resorption and...
May 18, 2007
Journal:
Osteoporos Int.
Author:
Henriksen K, Tankó LB, Qvist P, Delmas PD, Christiansen C, Karsdal MA
Although several treatments for osteoporosis exist, further understanding of the mode of action of current treatments, as well as development of novel treatments, are of interest. Thus, preclinical models of osteoporosis are very useful, as they provide the possibility for gaining knowledge about th...
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...
July 19, 2004
Journal:
J Bone Miner Res
Author:
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, Lichtengerg J, Christophersen P, Foged NT, Delaissé JM, Engsig MT, Karsdal MA
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