Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus

Søndergaard, B.C.; Catalá-Lehnen, Philip; Huebner, Antje K.; Bay‐Jensen, Anne‐Christine; Schinke, Thorsten; Henriksen, Kim; Schilling, Stefan; Haberland, Michael; Nielsen, Rasmus Hjorth; Amling, Michael; Karsdal, Morten A.

doi:10.1016/j.joca.2011.11.004

Cited by 32 publications

(28 citation statements)

References 50 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Administration of sCT significantly reduced CTX-2 levels in both SHAM and OVX animals 3 h after the final injection. This effect was greater in OVX animals, indicating that sCT may have protective effects on cartilage degradation, consistent with previous reports (Behets et al 2004, Bagger et al 2005, Sondergaard et al 2012. Administration of PTH in SHAM animals did not significantly alter CTX-2 levels, whereas in OVX animals PTH treatment significantly decreased CTX-2 levels.…”

Section: Resultssupporting

confidence: 90%

Decline in calcitonin receptor expression in osteocytes with age

Gooi

Chia

Walsh

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

We have previously shown that co-administration of the transient osteoclast inhibitor, salmon calcitonin (sCT), blunts the anabolic effect of parathyroid hormone (PTH) in young rats and increases osteocytic expression of the bone formation inhibitor sclerostin (Sost). To determine whether this also occurs in adult animals, we co-administered sCT with PTH to 6-month-old sham-operated (SHAM) and ovariectomised (OVX) rats. While sCT reduced the stimulatory effect of PTH on serum amino-terminal propeptide of type 1 procollagen levels, in contrast to its influence in young rats, sCT did not reduce the anabolic effect of PTH on femoral bone mineral density, tibial trabecular bone volume or bone formation rate in 6-month-old SHAM or OVX rats. Quantitative real-time PCR analysis of femoral metaphyses collected 1 and 4 h after a single PTH injection confirmed a significant increase in mRNA levels for interleukin 6 (Il6) and ephrinB2 (EfnB2), and a significant reduction in Sost and dentin matrix protein-1 (Dmp1) in response to PTH. However, in contrast to observations in young rats, these effects were not modified by co-administration of sCT, nor did sCT significantly modify Sost, Dmp1, or matrix extracellular phosphoglycoprotein (Mepe) mRNA levels. Furthermore, while CT receptor (CTR) mRNA (Calcr) was readily detected in GFPC osteocytes isolated from young (3-week-old) DMP1-GFP mice, Calcr levels in osteocytes declined as mice aged, reaching levels that were undetectable in long bone at 49 weeks of age. These data indicate that osteocyte-mediated responses to CT are most likely to be of physiological relevance in young rodents.

show abstract

Section: Resultssupporting

confidence: 90%

Decline in calcitonin receptor expression in osteocytes with age

Gooi

Chia

Walsh

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Further studies carried out in the canine Pond-Nuki model demonstrated that tiludronate exerts beneficial effects on gait disability and joint symptoms by improving some OA structural changes and reducing the synthesis of catabolic and inflammatory mediators [27]. Similar findings have been reported for calcitonin and estrogen use in different OA experimental models [16,[28][29][30][31][32][33][34][35][36][37][38][39][40]. Calcitonin prevented subchondral bone resorption and trabecular thinning associated to reduced cartilage degradation in a canine ACLT-induced OA model [28,29].…”

Section: Animal Studiessupporting

confidence: 65%

An OA phenotype may obtain major benefit from bone-acting agents

Roman‐Blas

Castañeda

Largo

et al. 2014

Seminars in Arthritis and Rheumatism

View full text Add to dashboard Cite

“…[48][49][50][51][52][53][54] In the DMM OA model on C57BL/6 mice, the DMM induced mechanical allodynia and activity obstacle coincidently with cartilage injury was found after 15 weeks of DMM surgery. Similar results also demonstrated by other groups, 26,39,55) but in their research, the slight pathological change on cartilage was found 9 weeks after the DMM surgery, different from 15 weeks in our DMM model.…”

Section: Discussionmentioning

confidence: 99%

The Therapeutic Effect of rhMK on Osteoarthritis in Mice, Induced by Destabilization of the Medial Meniscus

Zhu

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Osteoarthritis (OA) is a worldwide disease in aged people, causing not only physical suffering to the patients themselves, but also a great burden on their families and on society. Here we used a mouse OA model induced by destabilization of the medial meniscus (DMM), and studied the therapeutic effect of recombinant human midkine (rhMK) on this OA model. Our results indicated that the DMM surgery induced mechanical allodynia and locomotor activity obstacles, together with cartilage injury in the C57BL/6 mice. The rhMK treatment mitigated the OA related mechanical allodynia, improved locomotor activity capacity, and prevented degradation of the cartilage. Considering the safety issue of rhMK used as a biologic, we also inspected the main organs in the rhMK treated mice throughout the process and found no pathological change. These results suggest that rhMK could be used as a biologic to treat OA or OA related pain.

show abstract

Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus

Abstract: sCT over-expressing mice had higher bone volume, and were protected against cartilage erosion. These data suggest that increased levels of sCT may hamper the pathogenesis of osteoarthritis (OA). However more studies are necessary to confirm these preliminary results.

Cited by 32 publications

References 50 publications

Decline in calcitonin receptor expression in osteocytes with age

Decline in calcitonin receptor expression in osteocytes with age

An OA phenotype may obtain major benefit from bone-acting agents

The Therapeutic Effect of rhMK on Osteoarthritis in Mice, Induced by Destabilization of the Medial Meniscus

Contact Info

Product

Resources

About