Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells.

Sukhova, Galina K.; Shi, Guo Ping; Simon, Daniel I.; Chapman, Harold A.; Libby, Peter

doi:10.1172/jci181

Cited by 603 publications

(605 citation statements)

References 33 publications

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“…A series of factors have now been identified regulating connective tissue development in both the skeleton and vascular tissues 29. Cathepsin K, as well as being a lysosomal product of osteclasts with a key role in elastin and collagen degradation in bone,30 also plays a role in degrading vascular elastin, where overactivity leads to arterial aneurysm formation 31. In adult men and women, heritability studies have proposed shared genetic architecture underlying bone and vascular development 32.…”

Section: Discussionmentioning

confidence: 99%

Bone Mineral Density Is Positively Related to Carotid Intima-Media Thickness: Findings From a Population-Based Study in Adolescents and Premenopausal Women

Frysz

Deere

Lawlor

et al. 2016

Journal of Bone and Mineral Research

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Osteoporosis and cardiovascular disease (CVD) are both common causes of morbidity and mortality. Previous studies, mainly of people older than 60 years, suggest a relationship between these conditions. Our aim was to determine the association between bone characteristics and CVD markers in younger and middle‐aged individuals. Women (n = 3366) and their adolescent offspring (n = 4368) from the UK population‐based cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), were investigated. We measured total body (TB) and hip bone mineral density (BMD), TB bone area (BA) and bone mineral content (BMC) by dual‐energy X‐ray absorptiometry (DXA), and carotid intima‐media thickness (cIMT) by high‐resolution ultrasound. Arterial distensibility was calculated as the difference between systolic and diastolic arterial diameters. Linear regression determined associations between bone exposures and cIMT (in adolescents) and both cIMT and arterial distensibility (in women), generating partial correlation coefficients. Mean (SD) age of women was 48 (4.2) years, body mass index (BMI) was 26.2 (5.0) kg/m2, and 71% were premenopausal. In confounder‐adjusted analyses (age, height, lean mass, fat mass, menopause, smoking, estrogen replacement, calcium/vitamin D supplementation, and education) TB and hip BMD were both positively associated with cIMT (0.071 [0.030, 0.112], p = 0.001; 0.063 [0.025, 0.101], p = 0.001, respectively). Femoral neck BMD and TB BMD, BMC, and BA were positively associated with arterial distensibility. Mean (SD) age of adolescents was 17 (0.4) years, BMI was 23 (4.1) kg/m2, and 44.5% were male. Total hip and TB measurements were positively associated with cIMT, with similar magnitudes of association to those found in their mothers. In contrast to most published findings, we identified weak positive associations between BMD and cIMT in predominantly premenopausal women and their adolescent offspring. We found greater femoral neck BMD and TB DXA measurements to be associated with reduced arterial stiffness. Rather than a relationship with preclinical atherosclerosis, in these relatively young populations, we speculate our associations between BMD, cIMT, and arterial distensibility may reflect a shared relationship between bone and vascular growth and development. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Bone Mineral Density Is Positively Related to Carotid Intima-Media Thickness: Findings From a Population-Based Study in Adolescents and Premenopausal Women

Frysz

Deere

Lawlor

et al. 2016

Journal of Bone and Mineral Research

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“…Expression of cathepsin K has been shown in several cell populations like synovial fibroblasts (13), macrophages and smooth muscle cells in atheroma (27), various cell types of the lung (28), thyroid epithelial cells (29), and breast cancer cells (30). However, several studies indicate a predominant expression of cathepsin K in osteoclasts and osteoclast-like giant cells (12,14,15,(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

et al. 2001

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Cholesteatoma is a nonneoplastic lesion of the middle ear space or mastoid that is histologically characterized by a progressive bone erosion of the ossicles and surrounding bone. Several matrixdegrading enzymes have been implicated as mediators of this bone erosion. Because the novel cysteine proteinase cathepsin K has been shown to play a central role in bone resorption, we examined the expression of this enzyme in tissue specimens of cholesteatoma. Tissue specimens of 9 patients with cholesteatoma were obtained during middle-ear surgery. Expression of cathepsin K mRNA was determined by RT-PCR using specific primers. Immunohistochemical analysis of cathepsin K protein expression in tissue sections was performed by using the streptavidin-alkaline phosphatase technique. Expression of both cathepsin K mRNA and protein was detected in areas affected by cholesteatoma, whereas specimens of nonaffected ear cartilage and surrounding tissue were not positive. In addition, cathepsin K was detected in numerous multinucleated giant cells, particularly osteoclasts at the site of bone degradation. In contrast, keratinized squamous epithelium was negative for cathepsin K. These data demonstrate that the matrix-degrading cysteine proteinase cathepsin K may be involved in bone erosion in cholesteatoma. Strong expression of this collagenolytic enzyme in osteoclasts suggests that these cells are mainly involved in cathepsin K-mediated bone destruction.

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“…Expression of cathepsin K has been demonstrated in different cell populations like synovial fibroblasts (30), macrophages and smooth muscle cells in atheroma (31), and breast cancer cells (32). However, several studies indicate that cathepsin K is predominantly expressed in osteoclasts (27,33,34).…”

Section: Discussionmentioning

confidence: 99%

Expression of Cysteine Proteinases Cathepsins B and K and of Cysteine Proteinase Inhibitor Cystatin C in Giant Cell Tumor of Tendon Sheath

Hansen

Gäumann

et al. 2001

Modern Pathology

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The expression of cysteine proteinases cathepsins B and K and of the endogenous inhibitor of cysteine proteinases, cystatin C, was investigated in tissue specimens of patients with giant cell tumor of tendon sheath (GCTTS). Expression of both enzymes was examined by immunohistochemistry in tissue specimens of 14 patients with GCTTS. Applying double-labeling techniques, the coexpression of cathepsin B and its major endogenous inhibitor cystatin C was additionally studied. Cells expressing the respective proteins were further characterized with the macrophage markers HAM56 and anti-CD68 (clone PG-M1). Cathepsin B could be detected in numerous HAM56-positive mononuclear cells (MC), but only in very few giant cells (GC). In contrast, cathepsin K was predominantly identified in GC that were also strongly immunoreactive for cystatin C and CD68. Coexpression of cathepsin B and cystatin C occurred only in a few MC. The strong expression of both cathepsin B and K suggests that in GCTTS, bone erosion might be mediated not only by pressure of the proliferative tissue, but also by matrix-degrading cysteine proteinases. Because previous studies showed that osteoclasts express high levels of CD68, cathepsin K, and cystatin C but not of cathepsin B, our study contributes to the view that GC of GCTTS and osteoclasts are closely associated.

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Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells.

Cited by 603 publications

References 33 publications

Bone Mineral Density Is Positively Related to Carotid Intima-Media Thickness: Findings From a Population-Based Study in Adolescents and Premenopausal Women

Bone Mineral Density Is Positively Related to Carotid Intima-Media Thickness: Findings From a Population-Based Study in Adolescents and Premenopausal Women

Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

Expression of Cysteine Proteinases Cathepsins B and K and of Cysteine Proteinase Inhibitor Cystatin C in Giant Cell Tumor of Tendon Sheath

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