A novel in vivo model to study endochondral bone formation; HIF-1α activation and BMP expression

Emans, Pieter J.; Spaapen, Frank; Surtel, D.A.; Reilly, Keryn; Cremers, A.; Rhijn, Lodewijk W. van; Bulstra, Sjoerd K.; Voncken, Jan Willem; Kuijer, Roel

doi:10.1016/j.bone.2006.08.005

Cited by 53 publications

(50 citation statements)

References 43 publications

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“…Calcein green is a marker of mineralisation that, when injected, is incorporated in newly-formed bone for 24-36 h, while the unincorporated label is excreted by the kidneys within several hours (van Gaalen et al, 2010). In previous studies, we show that mineralisation during EO occurs about two weeks after initialisation of EO (Emans et al, 2005;Emans et al, 2007;Welting et al, 2011); therefore, the injection was performed at day 14 of the experiment (11 d before sacrifice). After 25 d, rabbits were euthanised by an overdose of intravenous pentobarbital.…”

Section: Methodsmentioning

confidence: 99%

“…During the same surgical procedure when the non-critical size defect was created, we used the method described by Emans and colleagues, for ectopically-inducing cartilage formation, in which a subperiosteal space is created to induce periosteal endochondral ossification (PEO) (Emans et al, 2007;Emans et al, 2010). PEO was induced on both tibia, as described in literature, with minor modifications (Emans et al, 2007;Emans et al, 2010).…”

Section: Periosteal Endochondral Ossificationmentioning

confidence: 99%

“…To further extend our knowledge on the influence of the COX-2 inhibitor celecoxib on the cartilaginous phase of EO, we tested it in three different in vivo compartments of the same rabbit. We studied EO during fracture healing of a non-critical size defect in the ulnae, in the growth plate and in ectopically-induced cartilaginous tissue (Emans et al, 2007;Emans et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase-2

Janssen

Caron

Rietbergen

et al. 2017

eCM

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Many studies have reported on the effects of cyclooxygenase-2 (COX-2) inhibition on osteogenesis. However, far less is known about the effects of COX-2 inhibition on chondrogenic differentiation. Previous studies conducted by our group show that COX-2 inhibition influences in vitro chondrogenic differentiation. Importantly, this might have consequences on endochondral ossification processes occurring in vivo, such as bone fracture healing, growth plate development and ectopic generation of cartilage. The goal of our study was to investigate, in vivo, the effect of COX-2 inhibition by celecoxib on the cartilaginous phase of three different endochondral ossification scenarios.10 mg/kg/d celecoxib or placebo were orally administered for 25 d to skeletally-immature New Zealand White rabbits (n = 6 per group). Endochondral ossification during fracture healing of a non-critical size defect in the ulna, femoral growth plate and ectopically-induced cartilaginous tissue were examined by radiography, micro-computed tomography (µ-CT), histology and gene expression analysis.Celecoxib treatment resulted in delayed bone fracture healing, alterations in growth plate development and progression of mineralisation. In addition, chondrogenic differentiation of ectopically-induced cartilaginous tissue was severely impaired by celecoxib. In conclusion, we found that celecoxib impaired the chondrogenic phase of endochondral ossification.

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Section: Methodsmentioning

confidence: 99%

Section: Periosteal Endochondral Ossificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase-2

Janssen

Caron

Rietbergen

et al. 2017

eCM

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“…Thus, it was not surprising that VEGFA expression was upregulated in wounds in which HO developed. A hypoxic environment during the early stages of endochondral bone formation is necessary for differentiation of progenitor cells toward chondrocyte lineage [14,38,50]. However, the final event in endochondral ossification and ectopic bone growth is replacement of the avascular cartilage template by highly vascularized bone.…”

Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Evans

Potter

Brown

et al. 2013

Clin Orthop Relat Res

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Background Heterotopic ossification (HO) is a frequent complication of modern wartime extremity injuries. The biological mechanisms responsible for the development of HO in traumatic wounds remain elusive. Question/purposes The aims of our study were to (1) characterize the expression profile of osteogenesis-related gene transcripts in traumatic war wounds in which HO developed; and (2) determine whether expression at the mRNA level correlated with functional protein expression and HO formation. Methods Biopsy specimens from 54 high-energy penetrating extremity wounds obtained at the initial and final surgical débridements were evaluated. The levels of selected osteogenic-related gene transcripts from RNA extracts were assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. As a result of its key role in osteogenesis, the concentration of BMP-2 in the effluent of 29 wounds also was determined. Conclusions Important differences exist in the osteogenic gene expression profile of wounds in which HO developed compared with wounds in which it did not develop. The upregulation of multiple osteogenesis-related gene transcripts indicates the presence of a proosteogenic environment necessary for ectopic bone formation in traumatic wounds.

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“…Activation of the hypoxic response can be essential for long bone formation [6][7][8][9] and enhances fracture repair 10 . Under hypoxia osteoblasts increase expression of vascular endothelial growth factor (VEGF), an angiogenic growth factor central to the establishment and repair of blood vessel networks 11 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of hypoxia-mimicking bioactive glasses for skeletal regeneration

et al. 2010

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The cellular response to hypoxia is vital for skeletal tissue development and regeneration. Numerous processes, including progenitor cell recruitment, proliferation and differentiation, are activated through the hypoxia pathway in a low oxygen pressure environment. Novel materials-based strategies designed to activate the hypoxia pathway are therefore of great interest for orthopaedic tissue engineering.Here resorbable bioactive glasses (BG) were designed to activate the hypoxia pathway by substitution of Co 2+ for Ca 2+ in the BG and substitution of Co 2+ and Ca 2+ /+2Na + for Si 4+ . This allowed for the controlled release of cobalt, whilst controlling BG bioactivity (apatite-forming ability). Two series of soda-lime-phosphosilicate glasses were manufactured with increasing concentrations of cobalt. Compositions were calculated to maintain constant network connectivity (2.13) by considering cobalt as an intermediate oxide in the first series, and as a network modifier in the second series. Mg 2+ and Zn 2+ were added to one of the Co 2+ -containing glasses to inhibit HCA formation since delay or inhibition of HCA formation is essential for the use of BG in soft tissues, as is the case of cartilage.Cobalt was present in both the silicate and phosphate phases of the BG. In addition, evidence was found for it playing a dual role in the silicate phase, acting as both an intermediate oxide and taking part in the network as well as being a network modifying oxide. Consistent with an intermediate oxide role, the presence of cobalt in the BG was shown to decrease ion release. HCA formation was delayed with cobalt additions. Mg 2+ and Zn 2+ further delayed HCA formation.Cobalt release was found to be proportional to cobalt content of the BGs enabling the controlled delivery of cobalt in therapeutic active doses.

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A novel in vivo model to study endochondral bone formation; HIF-1α activation and BMP expression

Cited by 53 publications

References 43 publications

Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase-2

Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase-2

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Synthesis and characterization of hypoxia-mimicking bioactive glasses for skeletal regeneration

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