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Journal of stem cells & regenerative medicine2017; 13(2); 45-53; doi: 10.46582/jsrm.1302008

Cathepsin K Localizes to Equine Bone In Vivo and Inhibits Bone Marrow Stem and Progenitor Cells Differentiation In Vitro.

Abstract: Selective inhibition of Cathepsin K (CatK) has a promising therapeutic potential for diseases associated with bone loss and osseous inflammation, such as osteoarthritis, periodontitis, and osteoporosis. In horses, stress-related bone injuries are common and accompanied by bone pain and inflammation resulting in excessive bone resorption and periostitis. VEL-0230 is a highly selective inhibitor of CatK that significantly decreased bone resorption and increased bone formation biomarkers. The goal of this study was to demonstrate the presence of CatK in equine bone and a simultaneous influence on the bone marrow cellular components including function and differentiation. Our objectives were: 1) to investigate the tissue localization of CatK protein in equine bone using immunohistochemistry, and 2) to determine the effect of CatK inhibition on osteoclastogenic, chondrogenic and osteogenic differentiation potential of equine stem and progenitor cells using histochemical staining and differentiation-related gene expression analyses. Bone biopsies, harvested from the tuber coxae and proximal phalanx of six healthy horses, were processed for immunostaining against CatK. Sternal bone marrow aspirates were cultured in 0, 1, 10, or 100 μM of VEL-0230 and subsequent staining scoring and gene expression analyses performed. All cells morphologically characterized as osteoclasts and moderate number of active bone lining osteoblasts stained positive for CatK. Histochemical staining and gene expression analyses revealed a significant increase in the osteoclastogenic, chondrogenic and osteogenic differentiation potential of equine bone marrow cells, which was VEL-0230-concentration dependent for the latter two. These results suggested that CatK inhibition may have anabolic effects on bone and cartilage regeneration that may be explained as a feedback response to CatK depletion. In conclusion, the use of CatK inhibition to reduce inflammation and associated bone resorption in equine osseous disorders may offer advantages to other therapeutics that would require further study.
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Publication Date: 2017-12-18 PubMed ID: 29391749PubMed Central: PMC5786646DOI: 10.46582/jsrm.1302008Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates how an inhibitor of Cathepsin K, a protein linked to bone loss and inflammation, may aid in treating equine bone injuries by enhancing bone and cartilage regeneration. The study examined where this protein is found in horse bones and the effect of its inhibition on various differentiation potentials of equine stem and progenitor cells.

Objective and Methodology

  • The primary objective of the study was to understand the effects of Cathepsin K (CatK) inhibition on bone marrow cellular components, focusing on their function and differentiation in equine bones.
  • Research was carried out in two stages, firstly locating CatK protein in equine bone via immunohistochemistry; secondly, studying the effects of CatK inhibition on the osteoclastogenic, chondrogenic, and osteogenic differentiation potential of equine stem and progenitor cells.
  • The study used VEL-0230, a selective inhibitor of CatK, and analyzed its concentration-dependent effects on cell differentiation.

Finding and Implications

  • Cells known as osteoclasts and a moderate number of bone-producing osteoblasts tested positive for CatK.
  • The analysis of VEL-0230 revealed a significant increase in the osteoclastogenic, chondrogenic, and osteogenic differentiation potential of equine bone marrow cells, indicating that CatK inhibition may enhance bone and cartilage regeneration.
  • The inhibitive action of VEL-0230 on CatK was found to be concentration-dependent for chondrogenic and osteogenic differentiation potentials.
  • The researchers suggest that the feedback response to CatK depletion due to the use of the inhibitor could explain these anabolic effects on bone and cartilage regeneration.
  • The use of CatK inhibition could deliver therapeutic benefits to treat inflammation and associated bone resorption in equine bones that might surpass other current therapies. However, more studies are needed to understand these potential benefits further.

Cite This Article

APA
Hussein H, Boyaka P, Dulin J, Russell D, Smanik L, Azab M, Bertone AL. (2017). Cathepsin K Localizes to Equine Bone In Vivo and Inhibits Bone Marrow Stem and Progenitor Cells Differentiation In Vitro. J Stem Cells Regen Med, 13(2), 45-53. https://doi.org/10.46582/jsrm.1302008

Publication

Journal of stem cells & regenerative medicine
ISSN: 0973-7154
NlmUniqueID: 101552911
Country: India
Language: English
Volume: 13
Issue: 2
Pages: 45-53

Researcher Affiliations

Hussein, Hayam
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Boyaka, Prosper
  • Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Dulin, Jennifer
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Russell, Duncan
  • Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Smanik, Lauren
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Azab, Mohamed
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Bertone, Alicia L
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
  • Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.

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