A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

Andreasen, Christina Møller; Ding, Ming; Overgaard, Søren; Bollen, Peter; Andersen, Thomas Levin

doi:10.1016/j.bone.2015.02.014

Cited by 33 publications

(35 citation statements)

References 41 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44 The lower level of cross-linking markers, such as cross-linked C-terminal telopeptide and NTX, was previously reported after 5 months of steroid treatment in OVX sheep. 21,45 The collagen catabolic process is indicated by CA2 relative expression in the spine, which was highest in the OVXD, whereas COL1A2 highest expression was in the OVXDS. The higher expression of COL1A2 indicates bone loss in osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Osteocyte Regulation of Receptor Activator of NF-κB Ligand/Osteoprotegerin in a Sheep Model of Osteoporosis

Khassawna

Merboth

Malhan

et al. 2017

The American Journal of Pathology

View full text Add to dashboard Cite

Osteoporosis induction in a sheep model by steroid administration combined with ovariectomy recapitulates decreased bone formation and substandard matrix mineralization in patients. Recently, the role of osteocytes has been frequently addressed, with focus on their role in osteoclastogenesis. However, the quantification of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) signaling in osteocytes was not studied in sheep. The current study reproduced the sheep model of osteoporosis to study the RANKL/OPG ratio correlation to the method of osteoporosis induction. We investigated the induction of osteoporosis after 8 months using 31 female merino land sheep divided into four groups: control, ovariectomy, ovariectomy with dietary limitation, and ovariectomy with dietary limitation and steroid injection. In accordance to previous reports, the present study showed trabecular thinning, higher numbers of apoptotic osteocytes, and imbalanced metabolism, leading to defective mineralization. The global RANKL/OPG ratio in the spine after 8 months of steroid and dietary treatment was not different from that of the control. Interestingly, assessment of the osteocyte-specific RANKL/OPG ratio showed that the steroid-induced osteoporosis in its late progressive phase stimulates RANKL expression in osteocytes. Sclerostin is suggested to induce RANKL expression in osteocytes. The findings of this study can contribute to further explain the success of sclerostin antibodies in treating osteoporotic patients despite increased osteocyte-expressed RANKL.

show abstract

Section: Discussionmentioning

confidence: 99%

Osteocyte Regulation of Receptor Activator of NF-κB Ligand/Osteoprotegerin in a Sheep Model of Osteoporosis

Khassawna

Merboth

Malhan

et al. 2017

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…For instance, recent studies have indicated that during the reversal phase of bone remodeling, canopy cells associated with osteoclasts are the source of pre‐osteoblasts necessary for bone formation . Furthermore, glucocorticoid treatment appears to reduce the association of canopy cells with osteoclasts which may underlie bone loss associated with glucocorticoid use and demonstrates that bone resorption and reversal can be de‐coupled . In fracture healing, osteoclasts may not be necessary for specifically resorbing the callus cartilage matrix but may be necessary for recruiting pre‐osteoblasts to the site of endochondral ossification as canopy cells.…”

Section: Discussionmentioning

confidence: 99%

Osteoclast depletion with clodronate liposomes delays fracture healing in mice

Hao

O’Connor

2016

J. Orthop. Res.

View full text Add to dashboard Cite

Osteoclasts are abundant within the fracture callus and also localize at the chondro-osseous junction. However, osteoclast functions during fracture healing are not well defined. Inhibition of osteoclast formation or resorptive activity impairs callus remodeling but does not prevent callus formation. Interestingly, though anti-osteoclast therapies differentially affect resolution of callus cartilage into bone. Treatments that inhibit osteoclast formation or viability tend to impair callus cartilage resolution, while treatments that target inhibition of bone resorption generally do not affect callus cartilage resolution. Here, we tested whether depletion of osteoclasts by systemic treatment with clodronate liposomes would similarly impair callus cartilage resolution. ICR mice were treated by intraperitoneal injections of clodronate-laden liposomes or control liposomes and subjected to closed femur fracture. Femurs were resected at multiple times after fracture and analyzed by radiography, histology, and mechanical testing to determine effects on healing. Clodronate liposome treatment did not prevent callus formation. However, radiographic scoring indicated that clodronate liposome treatment impaired healing. Clodronate liposome treatment significantly reduced callus osteoclast populations and delayed resolution of callus cartilage. Consistent with continued presence of callus cartilage, torsional mechanical testing found significant decreases in callus material properties after 28 days of healing. The results support a role for osteoclasts in the resolution of callus cartilage into bone. Whether the cartilage resolution role for osteoclasts is limited to simply resorbing cartilage at the chondro-osseous junction or in promoting bone formation at the chondro-osseous junction through another mechanism, perhaps similar to the reversal process in bone remodeling, will require further experimentation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1699-1706, 2017.

show abstract

“…The sheep is a frequently used model for orthopaedic research for several reasons: the bone size is large enough to perform complex orthopaedic procedures and for testing medical devices and biomaterials; the lifespan is short enough to perform age-related studies in diseases such as osteoarthritis and osteoporosis [16]; and their bone remodelling is comparable to that of humans [17]. Very little is known about A-CEAC for BTE.…”

Section: Introductionmentioning

confidence: 99%

Bone Formation by Sheep Stem Cells in an Ectopic Mouse Model: Comparison of Adipose and Bone Marrow Derived Cells and Identification of Donor‐Derived Bone by Antibody Staining

Kjærgaard

Dreyer

Ditzel

et al. 2016

Stem Cells International

Self Cite

View full text Add to dashboard Cite

Background. Scaffolds for bone tissue engineering (BTE) can be loaded with stem and progenitor cells (SPC) from different sources to improve osteogenesis. SPC can be found in bone marrow, adipose tissue, and other tissues. Little is known about osteogenic potential of adipose-derived culture expanded, adherent cells (A-CEAC). This study compares in vivo osteogenic capacity between A-CEAC and bone marrow derived culture expanded, adherent cells (BM-CEAC). Method. A-CEAC and BM-CEAC were isolated from five female sheep and seeded on hydroxyapatite granules prior to subcutaneous implantation in immunodeficient mice. The doses of cells in the implants were 0.5 × 106, 1.0 × 106, or 1.5 × 106 A-CEAC and 0.5 × 106 BM-CEAC, respectively. After eight weeks, bone volume versus total tissue volume (BV/TV) was quantified using histomorphometry. Origin of new bone was assessed using human vimentin (HVIM) antibody staining. Results. BM-CEAC yielded significantly higher BV/TV than any A-CEAC group, and differences between A-CEAC groups were not statistically significant. HVIM antibody stain was successfully used to identify sheep cells in this model. Conclusion. A-CEAC and BM-CEAC were capable of forming bone, and BM-CEAC yielded significantly higher BV/TV than any A-CEAC group. In vitro treatment to enhance osteogenic capacity of A-CEAC is suggested for further research in ovine bone tissue engineering.

show abstract

A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

Cited by 33 publications

References 41 publications

Osteocyte Regulation of Receptor Activator of NF-κB Ligand/Osteoprotegerin in a Sheep Model of Osteoporosis

Osteocyte Regulation of Receptor Activator of NF-κB Ligand/Osteoprotegerin in a Sheep Model of Osteoporosis

Osteoclast depletion with clodronate liposomes delays fracture healing in mice

Bone Formation by Sheep Stem Cells in an Ectopic Mouse Model: Comparison of Adipose and Bone Marrow Derived Cells and Identification of Donor‐Derived Bone by Antibody Staining

Contact Info

Product

Resources

About