Osteoclasts secrete non-bone derived signals that induce bone formation

Karsdal, Morten A.; Neutzsky-Wulff, Anita V.; Dziegiel, Morten Hanefeld; Christiansen, Claus; Henriksen, Kim

doi:10.1016/j.bbrc.2007.11.168

Cited by 97 publications

(60 citation statements)

References 38 publications

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“…This definition acknowledges regulatory (autocrine/ paracrine/endocrine) pathways within bone remodeling and also points to the fact that bone formation is ongoing in osteopetrosis. For ADO, the defective osteoclasts seem to regulate bone formation (75,81,96). This updated definition is also in alignment with the original description of the naturally occurring murine forms of osteopetrosis, depicting osteoclast-poor (ex the tl-rat, (151, 158, 159)) and -rich forms (ex the ia-rat, (211,212)).…”

Section: Updated Definition Of Clinical Osteopetrosissupporting

confidence: 54%

“…In accordance with these studies, a series of in vitro studies of osteoclasts have shown that independent of their resorptive activity, osteoclasts produce anabolic signals for osteoblasts (69,75,76,77), thus explaining the origin of the ongoing bone formation in the ADO/osteoclast-rich osteopetrosis patients, see Fig. 3.…”

Section: Analysis Of Osteoclasts From Ado Patientsmentioning

confidence: 54%

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Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Bollerslev

Henriksen

Nielsen

et al. 2013

European Journal of Endocrinology

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Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the first propeller of LRP5, a region of importance for binding inhibitory proteins. Thereby, ADO1 cannot be regarded as a classical form of osteopetrosis but must now be considered a disease of LRP5 activation. ADO (Albers-Schönberg disease, or previously ADO2) is characterized by increased number of osteoclasts and a defect in the chloride transport system (ClC-7) of importance for acidification of the resorption lacuna (a form of Chloride Channel 7 Deficiency Osteopetrosis). Ex vivo studies of osteoclasts from ADO have shown that cells do form normally but have reduced resorption capacity and an expanded life span. Bone formation seems normal despite decreased osteoclast function. Uncoupling of formation from resorption makes ADO of interest for new strategies for treatment of osteoporosis. Recent studies have integrated bone metabolism in whole-body energy homeostasis. Patients with ADO may have decreased insulin levels indicating importance beyond bone metabolism. There seems to be a paradigm shift in the treatment of osteoporosis. Targeting ClC-7 might introduce a new principle of dual action. Drugs affecting ClC-7 could be antiresorptive, still allowing ongoing bone formation. Inversely, drugs affecting the inhibitory site of LRP5 might stimulate bone formation and inhibit resorption. Thereby, these studies have highlighted several intriguing treatment possibilities, employing novel modes of action, which could provide benefits to the treatment of osteoporosis.

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Section: Updated Definition Of Clinical Osteopetrosissupporting

confidence: 54%

Section: Analysis Of Osteoclasts From Ado Patientsmentioning

confidence: 54%

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Bollerslev

Henriksen

Nielsen

et al. 2013

European Journal of Endocrinology

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“…Given no clear evidence of osteoclast resorption and depleted Ca 2+ /P i levels in the conditioned medium, we speculate that the osteogenic effects were most likely due to osteoclast-secreted trophic factors in response to the submicrostructured surface topography. In a broader biological context, it is pertinent to note that non-resorbing osteoclasts have been identified as a source of osteogenic factors in vivo (Karsdal et al, 2007;Karsdal et al, 2008;Kreja et al, 2010), emphasising that resorption is not necessary for osteogenic signalling (Fuller et al, 2010), potentially an interesting link for non-resorbable, osteoinductive materials such as microstructured titanium. Concerning the interspecies potency of the osteogenic factors demonstrated here, Pederson et al (2008) first reported that RAW264.7 osteoclast-like cells secrete soluble sphingosine 1 phosphate (S1P) and BMP6 which can differentiate hMSC into mineralising osteoblasts.…”

Section: Nl Davison Et Al Surface Architecture Of Tricalcium Phosphatementioning

confidence: 99%

Submicron-scale surface architecture of tricalcium phosphate directs osteogenesis in vitro and in vivo

Davison

Luo²,

Schoenmaker³

et al. 2014

eCM

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A current challenge of synthetic bone graft substitute design is to induce bone formation at a similar rate to its biological resorption, matching bone's intrinsic osteoinductivity and capacity for remodelling. We hypothesise that both osteoinduction and resorption can be achieved by altering surface microstructure of beta-tricalcium phosphate (TCP). To test this, two TCP ceramics are engineered with equivalent chemistry and macrostructure but with either submicron-or micron-scale surface architecture. In vitro, submicron-scale surface architecture differentiates larger, more active osteoclasts -a cell type shown to be important for both TCP resorption and osteogenesis -and enhances their secretion of osteogenic factors to induce osteoblast differentiation of human mesenchymal stem cells. In an intramuscular model, submicrostructured TCP forms 20 % bone in the free space, is resorbed by 24 %, and is densely populated by multinucleated osteoclast-like cells after 12 weeks; however, TCP with micron-scale surface architecture forms no bone, is essentially not resorbed, and contains scarce osteoclast-like cells. Thus, a novel submicron-structured TCP induces substantial bone formation and is resorbed at an equivalent rate, potentially through the control of osteoclast-like cells.

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“…The widely accepted view is that osteoclasts can promote the differentiation of osteoblasts. Conditioned medium derived from human osteoclasts induces preosteoblasts to form bonelike nodules (6). Gene array analysis, in combination with loss-of-function studies, revealed that mature osteoclasts secrete Wnt10b, sphingosine 1-phosphate, and bone morphogenetic protein-6 (BMP6) and might promote osteoblast mineralization (7).…”

Section: Introductionmentioning

confidence: 99%

Osteogenic differentiation of human ligament fibroblasts induced by conditioned medium of osteoclast-like cells

Cui

Zhou

et al. 2011

BST

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Osteoclasts secrete non-bone derived signals that induce bone formation

Cited by 97 publications

References 38 publications

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Submicron-scale surface architecture of tricalcium phosphate directs osteogenesis in vitro and in vivo

Osteogenic differentiation of human ligament fibroblasts induced by conditioned medium of osteoclast-like cells

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