Immunohistochemical Localization of RANK, RANKL and OPG in Healthy and Arthritic Canine Elbow Joints

Spahni, Andrea I.; Schawalder, Peter; Rothen, Barbara; Bosshardt, Dieter D.; Lang, Niklaus P.; Stoffel, Michael

doi:10.1111/j.1532-950x.2009.00566.x

Cited by 5 publications

(12 citation statements)

References 26 publications

(38 reference statements)

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“…OPG is expressed and produced by many cell types. It was reported that human chondrocytes and annulus fibrosus of IVD express OPG and RANKL [7–9]. However, the effect of OPG on IVDs has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice

Qian

Zhou

et al. 2011

Bone

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Objective Human chondrocytes and annulus fibrosus cells of intervertebral disc (IVD) express osteoprotegerin (OPG), but the effect of OPG on the pathogenesis of IVD degeneration remains unknown. Here we assessed the phenotype change of IVD in OPG−/− mice. Methods The IVDs from 12-, 20-, and 28-week-old OPG−/− mice and WT controls were subjected to histologic analyses including TRAP staining for osteoclasts, immunostaining for OPG and type I collagen protein expression, and TUNEL staining for apoptosis. The IVD tissues were also subjected to real time RT-PCR for mRNA expression of genes for osteoblast-osterix, ALP, and osteocalcin; for osteoclasts-trap, rank, mmp9 and cathepsin K, and for chondrocytes-aggrecan, mmp13 and Col10. Results OPG protein expresses at the cells of endplate cartilage and annulus fiborsis in IVDs of WT mice. Compared to WT mice, OPG−/− mice developed aging related cartilage loss and bony tissue appearance at the endplate. Stating from 20 weeks of age, IVDs from OPG−/− mice expressed significantly increased mmp13 and Col10 levels, which is associated with increased osteoblast number and elevated expression of osteoblast marker genes. Furthermore, TRAP+ osteoclasts were presented in the endplate cartilage of OPG−/− mice. These osteoclasts localized adjacently to and erosion into the cartilage. Increased expression of RANK, mmp9 and cathepsin k was detected in OPG−/− IVDs. Conclusions OPG at IVD plays an important role for maintaining the integrity of endplate cartilage during aging by preventing endplate cartilage from osteoclast-mediated resorption.

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Section: Introductionmentioning

confidence: 99%

The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice

Qian

Zhou

et al. 2011

Bone

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“…33 This moderate crossreactivity in specific locations did not interfere with interpretation of results as corresponding structures were clearly distinct from the regions and tissues of interest. However, weak immunostaining of epithelial tissue, blood vessels, and dental calculus was observed.…”

Section: Resultsmentioning

confidence: 98%

“…33 Although no complete sets of serial sections were available, fullsize transverse sections enabled a comprehensive assessment of the teeth and periodontal ligament. 33 Although no complete sets of serial sections were available, fullsize transverse sections enabled a comprehensive assessment of the teeth and periodontal ligament.…”

Section: Resultsmentioning

confidence: 99%

“…33 Two of 8 cats showed no radiographic or histopathologic signs of tooth resorption. Similarly, immunostaining was absent when rabbit anti-CS3 antibody, rabbit anti-calcitonin, and mouse anti-CFA/I antibodies were used as irrelevant substitutes for corresponding primary antibodies.…”

Section: The Resorption Front (Inset) Is Lined By Multinucleated Cellmentioning

confidence: 93%

“…33 Control experiments included omission of primary antibody and omission of both the primary as well as the secondary antibody. 33 Control experiments included omission of primary antibody and omission of both the primary as well as the secondary antibody.…”

Section: Methodsmentioning

confidence: 99%

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Immunohistochemical Localization of Osteoclastogenic Cell Mediators in Feline Tooth Resorption and Healthy Teeth

et al. 2010

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Tooth resorption is among the most common and most challenging problems in feline dentistry. It is a progressive disease eventually leading to tooth loss and often root replacement. The etiology of tooth resorption remains obscure and to date no effective therapeutic approach is known. The present study is aimed at assessing the reliability of radiographic imaging and addressing the possible involvement of receptor activator of NFκB (RANK), its ligand (RANKL), and osteoprotegerin (OPG) in the process of tooth resorption. Teeth from 8 cats were investigated by means of radiographs and paraffin sections followed by immunolabeling. Six cats were diagnosed with tooth resorption based on histopathologic and radiographic findings. Samples were classified according to a four-stage diagnostic system. Radiologic assessment of tooth resorption correlated very strongly with histopathologic findings. Tooth resorption was accompanied by a strong staining with all three antibodies used, especially with anti-RANK and anti-RANKL antibodies. The presence of OPG and RANKL at the resorption site is indicative of repair attempts by fibroblasts and stromal cells. These findings should be extended by further investigations in order to elucidate the pathophysiologic processes underlying tooth resorption that might lead to prophylactic and/or therapeutic measures.

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Multiloculated solitary (unicameral) bone cyst in a young dog

Roode

Shive

Hoorntje

et al. 2018

Veterinary Clinical Pathol

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A 20-month-old female spayed Staffordshire Terrier (22.3 kg) presented to the Orthopedic Surgery Service at North Carolina State University Veterinary Teaching Hospital for evaluation of a 6-week history of toe-touching to nonweight-bearing lameness in the right hind limb. Radiographs of the right stifle revealed a multiloculated lytic lesion of the distal femur, with a large open lytic zone centrally, numerous osseous septations peripherally, and focal areas of cortical thinning and loss. An aspirate of the right distal femoral lesion yielded mildly cloudy serosanguineous fluid. Cytologic examination of the fluid revealed a pleomorphic population of discrete cells that exhibited marked anisocytosis and anisokaryosis and a variable nuclear-to-cytoplasmic (N:C) ratio, which were interpreted as probable neoplastic cells, with few macrophages, and evidence of hemorrhage. Given the clinical signs of pain, lesion size, and concern for malignant neoplasia, amputation of the right hind limb was performed. Histologically, the lesion had undulating walls 1-3 mm thick with a continuous outer layer of dense fibrous tissue and an inner layer composed of reactive cancellous bone with no cortical compacta remaining. Remnants of thin fibrous or fibro-osseous septa projected from the bony wall into the cyst lumen. The final histologic diagnosis was a benign multiloculated solitary (unicameral) bone cyst of the distal right femur. Based on the histopathologic findings, it was speculated that the cells identified on cytology were a mixture of developing osteoclasts, osteoblasts, endothelial, and stromal cells. This is the first report describing the cytologic examination of a solitary bone cyst in veterinary medicine.

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Immunohistochemical Localization of RANK, RANKL and OPG in Healthy and Arthritic Canine Elbow Joints

Abstract: Therapeutic use of neutralizing antibodies against RANKL to inhibit osteoclast activation warrants further investigation.

Cited by 5 publications

References 26 publications

The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice

The expression of osteoprotegerin is required for maintaining the intervertebral disc endplate of aged mice

Immunohistochemical Localization of Osteoclastogenic Cell Mediators in Feline Tooth Resorption and Healthy Teeth

Multiloculated solitary (unicameral) bone cyst in a young dog

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