Effects of an inhibitor of cathepsin L on bone resorption in thyroparathyroidectomized and ovariectomized rats

Millest, Andrew J.; Breen, S. A.; Loveday, Bernard E.; Clarkson, PM; Simpson, Christine; Waterton, John C.; Johnstone, D

doi:10.1016/s8756-3282(97)00014-8

“…It was shown that the use of cathepsin L inhibitors reduced cortical bone mineral density and results in inhibition of bone resorption in thyroparathyroidectomized and ovariectomized rats [139]. In cathepsin L knockout mice loss of trabecular bone following ovariectomy occurred to a lesser extent in homozygote and heterozygote mice than in the wild-type mice [140].…”

Section: Osteoporosismentioning

confidence: 99%

Emerging Roles of Cysteine Cathepsins in Disease and their Potential as Drug Targets

Vasiljeva

¹

,

Reinheckel²,

Peters³

et al. 2007

CPD

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The general view on cysteine cathepsins, which were long believed to be primarily involved in intracellular protein turnover, has dramatically changed in last 10 to 15 years. The discovery of new cathepsins, such as cathepsins K, V, X, F and O, and their tissue distribution suggested that at least some of them are involved in very specific cellular processes. Moreover, gene ablation experiments revealed that cathepsins play a vital role in numerous physiological processes, such as antigen processing and presentation, bone remodelling, prohormone processing and wound healing. Their involvement in several pathologies, including osteoporosis, rheumatoid arthritis, osteoarthritis, bronchial asthma and cancer have also been confirmed and today several of them have been validated as relevant targets for therapies. Compounds targeting cathepsins S and K are already in clinical evaluation, whereas others are in experimental phases. The cathepsin K inhibitor AAE-581 (balicatib) as the most advanced of them passed Phase II clinical trials in 2005. In this review, we discuss the current view on cathepsins as an emerging group of targets for several diseases and the development of cathepsin K and S inhibitors for treatment of osteoporosis and various immune disorders.

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“…In animal studies, the association between cathepsin L inhibitors, reduced BMD, and inhibition of bone resorption was identified [117,118].…”

Section: Cathepsin K Inhibitorsmentioning

confidence: 99%

“…It was observed that in orchidectomized animals bone loss is accelerated. Aromatase activity as a converting enzyme (androgen to estrogen) was discovered in bone [117] and its deficiency in mice increased bone loss [118]. Testosterone has different physiologic functions in human, while selective androgen receptor modulators (SARMs) are acting more tissue-specific.…”

Section: Sarmsmentioning

confidence: 99%

Current, new and future treatments of osteoporosis

Salari

¹

,

Abdollahi

²

,

Larijani

³

2010

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Osteoporosis as a common chronic disease is challenging human health. Although different therapeutic options are routinely used for prevention/treatment of osteoporosis, their side effects and benefits are under question. Increasing our knowledge about signaling pathways in bone and osteocytes as well as osteoblasts and osteoclasts will help us in designing new therapeutic modalities for osteoporosis. In the present study, all new therapeutic measures of osteoporosis have been reviewed. For this purpose, search engines like Pubmed, Web of Science, Scopus, Google Scholar were searched and all relevant articles were found. The study was limited to the year 1998-2010. Bisphosphonates are the cornerstone of osteoporosis treatment, but there are not enough relevant studies that investigated their equivalencies in comparison with each other or the other medications. Therefore, medication selection is empirical and subjective. Furthermore, no eminent study has compared certain combinations. There are new hopes for treatment of osteoporosis, which are more specific with less harm. Our results show that new and emerging therapies are more potent and target specified which more individualize osteoporosis treatment; however, more investigations on their safety and efficacy in comparison with current medications are highly recommended.

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“…It was shown that the use of cathepsin L inhibitors reduced cortical bone mineral density and results in inhibition of bone resorption in thyroparathyroidectomized and ovariectomized rats [139]. It was shown that the use of cathepsin L inhibitors reduced cortical bone mineral density and results in inhibition of bone resorption in thyroparathyroidectomized and ovariectomized rats [139].…”

Section: Osteoporosismentioning

confidence: 99%

Emerging Roles of Cysteine Cathepsins in Disease and their Potential as Drug Targets

Vasiljeva¹,

Reinheckel²,

Peters³

et al. 2007

View full text Add to dashboard Cite

The general view on cysteine cathepsins, which were long believed to be primarily involved in intracellular protein turnover, has dramatically changed in last 10 to 15 years. The discovery of new cathepsins, such as cathepsins K, V, X, F and O, and their tissue distribution suggested that at least some of them are involved in very specific cellular processes. Moreover, gene ablation experiments revealed that cathepsins play a vital role in numerous physiological processes, such as antigen processing and presentation, bone remodelling, prohormone processing and wound healing. Their involvement in several pathologies, including osteoporosis, rheumatoid arthritis, osteoarthritis, bronchial asthma and cancer have also been confirmed and today several of them have been validated as relevant targets for therapies. Compounds targeting cathepsins S and K are already in clinical evaluation, whereas others are in experimental phases. The cathepsin K inhibitor AAE-581 (balicatib) as the most advanced of them passed Phase II clinical trials in 2005. In this review, we discuss the current view on cathepsins as an emerging group of targets for several diseases and the development of cathepsin K and S inhibitors for treatment of osteoporosis and various immune disorders.

show abstract

Effects of an inhibitor of cathepsin L on bone resorption in thyroparathyroidectomized and ovariectomized rats

Cited by 15 publications

References 35 publications

Emerging Roles of Cysteine Cathepsins in Disease and their Potential as Drug Targets

Emerging Roles of Cysteine Cathepsins in Disease and their Potential as Drug Targets

Current, new and future treatments of osteoporosis

Emerging Roles of Cysteine Cathepsins in Disease and their Potential as Drug Targets

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