Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis?
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease involving both bone and cartilage properties, and may therefore require alternative approaches for treatment. Recent lines o…
Journal:
Authors:
- Karsdal MA,
- Sondergaard BC,
- Arnold M,
- Christiansen C,
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,
Osteoarthritic cartilage is more homogeneous than healthy cartilage: identification of a superior region of interest colocalized with a major risk factor for osteoarthritis
RATIONALE AND OBJECTIVES:
Cartilage loss as determined by magnetic resonance imaging (MRI) or joint space narrowing as determined by x-ray is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more sensitive assessment met…
Journal:
Authors:
- Qazi AA,
- Dam EB,
- Nielsen M,
- Karsdal MA,
- Pettersen PC,
- Christiansen C,
Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival
Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased osteo…
Journal:
Authors:
- Nielsen RH,
- Karsdal MA,
- Sørensen MG,
- Dziegiel MH,
- Henriksen K,
The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model
OBJECTIVE:
To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats.
METHODS:
Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-…
Journal:
Authors:
- Sondergaard BC,
- Oestergaard S,
- Christiansen C,
- Tankó LB,
- Karsdal MA,
Bone, cartilage and hormone therapy: established concepts and future scenarios
In the aftermath of the Women's Health Initiative (WHI) study, the firm ground of postmenopausal hormone therapy (HT) has been thoroughly shaken. While there was agreement that HT is indicated for the therapy of menopause-associated vasomotor symptoms and vulvovaginal atrophy, there was a general an…
Journal:
Authors:
- Holinka CF,
- Karsdal MA,
- Christiansen C,
Osteoclasts prefer aged bone
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…
Journal:
Authors:
- Henriksen K,
- Leeming DJ,
- Byrjalsen I,
- Nielsen RH,
- Sorensen MG,
- Dziegiel MH,
- Martin TJ,
- Christiansen C,
- Qvist P,
- Karsdal MA,
Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation
OBJECTIVE:
Calcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective.
METHODS:
Cartilage degradation was i…
Journal:
Authors:
- Karsdal MA,
- Sumer EU,
- Wulf H,
- Madsen SH,
- Christiansen C,
- Fosang AJ,
- Sondergaard BC,
Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases
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…
Journal:
Authors:
- Henriksen K,
- Tankó LB,
- Qvist P,
- Delmas PD,
- Christiansen C,
- Karsdal MA,
Characterization of osteoclasts derived from CD14+ monocytes isolated from peripheral blood
Bone resorption is solely mediated by osteoclasts. Therefore, a pure osteoclast population is of high interest for the investigation of biological aspects of the osteoclasts, such as the direct effect of growth factors and hormones, as well as for testing and characterizing inhibitors of bone resorp…
Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Schaller S,
- Henriksen DB,
- Nielsen FC,
- Dziegiel MH,
- Karsdal MA,
Biochemical markers in preclinical models of osteoporosis
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…
Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Schaller S,
- Karsdal MA,
Separation of healthy and early osteoarthritis by automatic quantification of cartilage homogeneity
OBJECTIVE:
Cartilage loss as determined either by magnetic resonance imaging (MRI) or by joint space narrowing in X-rays is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more accurate assessment method for early chang…
Journal:
Authors:
- Qazi AA,
- Folkesson J,
- Karsdal MA,
- Christiansen C,
- Dam EB,
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,
Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen
The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo.
DESIGN:
Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis fac…
Journal:
Authors:
- Olsen AK,
- Sondergaard BC,
- Byrjalsen I,
- Tankó LB,
- Christiansen C,
- Müller A,
- Hein GE,
- Karsdal MA,
- Qvist P,
MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan assays
Aggrecan is the major proteoglycan in articular cartilage and is known to be degraded by various proteases, including matrix metalloproteinases (MMPs). The present study was undertaken to develop immunoassays detecting aggrecan and its fragments generated by MMP and non-MMP-mediated proteolysis.
…
Journal:
Authors:
- Sumer EU,
- Sondergaard BC,
- Rousseau JC,
- Delmas PD,
- Fosang AJ,
- Karsdal MA,
- Christiansen C,
- Qvist P,