Diverse Response to Local Pharmacological Blockade of Sirt1 Cleavage in Age-Induced versus Trauma-Induced Osteoarthritis Female Mice Article Swipe
Yonathan H. Maatuf
,
Miya Marco
,
Shani Unger-Gelman
,
Eli Farhat
,
Anna Zobrab
,
Ankita Roy
,
Ashish Kumar
,
Idan Carmon
,
Eli Reich
,
Mona Dvir‐Ginzberg
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3390/biom14010081
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3390/biom14010081
Objective: Previous studies have shown that the cleavage of Sirt1 contributes to the development of osteoarthritis (OA). In fact, OA was effectively abrogated by the intra-articular (IA) administration of two compounds, one blocking Sirt1 cleavage (CA074me) and the other activating Sirt1 (SRT1720), using a post-traumatically induced model (PTOA) in young female mice. In this study, we attempted to understand if this local treatment is effective in preventing age-associated OA (AOA) progression and symptoms. Design: A group of 17-month-old female C57BL/6J mice were IA administered with CA074me and/or SRT1720 or their combination. Joint histopathological analysis and bone histomorphometry were carried out, with an assessment of knee mechanical hyperalgesia. A serum analysis for NT/CT Sirt1 was carried out along with immunohistochemistry for articular cartilage to detect p16INK4A or γH2A.X. Similarly, meniscal cartilage was monitored for Lef1 and Col1a1 deposition. The data were compared for young female mice subjected to post-traumatic OA (PTOA). Results: Similar to PTOA, combination-treated AOA exhibited improved knee hyperalgesia, yet structural improvements were undetected, corresponding to unchanged NT/CT Sirt1 serum levels. Both AOA and PTOA exhibited unchanged staining for nuclear p16INK4A or γH2A.X and lacked a correlation with OA severity. Contrarily to PTOA, the combination treatment with AOA did not exhibit a local reduction in the Lef1 and Col1 targets. Conclusions: When targeting Sirt1 cleavage, the PTOA and AOA models exhibited a similar pain response to the combination treatment; however, they displayed diverse structural outcomes for joint-related damage, related to Lef1-dependent signaling. Interestingly, nuclear p16INK4A was unaffected in both models, regardless of the treatment’s effectiveness. Finally, these findings highlight the variations in the responses between two highly researched OA preclinical models, reflecting OA pathophysiology heterogeneity and variations in gender-related drug-response mechanisms.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/biom14010081
- https://www.mdpi.com/2218-273X/14/1/81/pdf?version=1704713202
- OA Status
- gold
- Cited By
- 2
- References
- 34
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4390662491
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4390662491Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/biom14010081Digital Object Identifier
- Title
-
Diverse Response to Local Pharmacological Blockade of Sirt1 Cleavage in Age-Induced versus Trauma-Induced Osteoarthritis Female MiceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-01-08Full publication date if available
- Authors
-
Yonathan H. Maatuf, Miya Marco, Shani Unger-Gelman, Eli Farhat, Anna Zobrab, Ankita Roy, Ashish Kumar, Idan Carmon, Eli Reich, Mona Dvir‐GinzbergList of authors in order
- Landing page
-
https://doi.org/10.3390/biom14010081Publisher landing page
- PDF URL
-
https://www.mdpi.com/2218-273X/14/1/81/pdf?version=1704713202Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.mdpi.com/2218-273X/14/1/81/pdf?version=1704713202Direct OA link when available
- Concepts
-
Osteoarthritis, Medicine, Cartilage, Immunohistochemistry, Type II collagen, Internal medicine, Hyperalgesia, Endocrinology, Pathology, Anatomy, Nociception, Receptor, Alternative medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1, 2024: 1Per-year citation counts (last 5 years)
- References (count)
-
34Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.PTOA | 175, 217 |
| abstract_inverted_index.When | 212 |
| abstract_inverted_index.bone | 95 |
| abstract_inverted_index.both | 249 |
| abstract_inverted_index.data | 138 |
| abstract_inverted_index.have | 3 |
| abstract_inverted_index.knee | 104, 158 |
| abstract_inverted_index.mice | 80, 144 |
| abstract_inverted_index.out, | 99 |
| abstract_inverted_index.pain | 224 |
| abstract_inverted_index.that | 5 |
| abstract_inverted_index.they | 231 |
| abstract_inverted_index.this | 53, 60 |
| abstract_inverted_index.were | 81, 97, 139, 163 |
| abstract_inverted_index.with | 84, 100, 117, 188, 197 |
| abstract_inverted_index.(AOA) | 69 |
| abstract_inverted_index.(OA). | 16 |
| abstract_inverted_index.Joint | 91 |
| abstract_inverted_index.NT/CT | 111, 168 |
| abstract_inverted_index.PTOA, | 153, 193 |
| abstract_inverted_index.Sirt1 | 9, 33, 40, 112, 169, 214 |
| abstract_inverted_index.along | 116 |
| abstract_inverted_index.fact, | 18 |
| abstract_inverted_index.group | 75 |
| abstract_inverted_index.local | 61, 203 |
| abstract_inverted_index.mice. | 51 |
| abstract_inverted_index.model | 46 |
| abstract_inverted_index.other | 38 |
| abstract_inverted_index.serum | 108, 170 |
| abstract_inverted_index.shown | 4 |
| abstract_inverted_index.their | 89 |
| abstract_inverted_index.these | 257 |
| abstract_inverted_index.using | 42 |
| abstract_inverted_index.young | 49, 142 |
| abstract_inverted_index.(PTOA) | 47 |
| abstract_inverted_index.Col1a1 | 135 |
| abstract_inverted_index.and/or | 86 |
| abstract_inverted_index.detect | 123 |
| abstract_inverted_index.female | 50, 78, 143 |
| abstract_inverted_index.highly | 267 |
| abstract_inverted_index.lacked | 185 |
| abstract_inverted_index.models | 220 |
| abstract_inverted_index.study, | 54 |
| abstract_inverted_index.(PTOA). | 149 |
| abstract_inverted_index.CA074me | 85 |
| abstract_inverted_index.Design: | 73 |
| abstract_inverted_index.SRT1720 | 87 |
| abstract_inverted_index.Similar | 151 |
| abstract_inverted_index.between | 265 |
| abstract_inverted_index.carried | 98, 114 |
| abstract_inverted_index.damage, | 238 |
| abstract_inverted_index.diverse | 233 |
| abstract_inverted_index.exhibit | 201 |
| abstract_inverted_index.induced | 45 |
| abstract_inverted_index.levels. | 171 |
| abstract_inverted_index.models, | 250, 271 |
| abstract_inverted_index.nuclear | 180, 244 |
| abstract_inverted_index.related | 239 |
| abstract_inverted_index.similar | 223 |
| abstract_inverted_index.studies | 2 |
| abstract_inverted_index.γH2A.X | 183 |
| abstract_inverted_index.C57BL/6J | 79 |
| abstract_inverted_index.Finally, | 256 |
| abstract_inverted_index.Previous | 1 |
| abstract_inverted_index.Results: | 150 |
| abstract_inverted_index.analysis | 93, 109 |
| abstract_inverted_index.blocking | 32 |
| abstract_inverted_index.cleavage | 7, 34 |
| abstract_inverted_index.compared | 140 |
| abstract_inverted_index.findings | 258 |
| abstract_inverted_index.however, | 230 |
| abstract_inverted_index.improved | 157 |
| abstract_inverted_index.meniscal | 128 |
| abstract_inverted_index.outcomes | 235 |
| abstract_inverted_index.p16INK4A | 124, 181, 245 |
| abstract_inverted_index.response | 225 |
| abstract_inverted_index.staining | 178 |
| abstract_inverted_index.targets. | 210 |
| abstract_inverted_index.γH2A.X. | 126 |
| abstract_inverted_index.(CA074me) | 35 |
| abstract_inverted_index.abrogated | 22 |
| abstract_inverted_index.articular | 120 |
| abstract_inverted_index.attempted | 56 |
| abstract_inverted_index.cartilage | 121, 129 |
| abstract_inverted_index.cleavage, | 215 |
| abstract_inverted_index.displayed | 232 |
| abstract_inverted_index.effective | 64 |
| abstract_inverted_index.exhibited | 156, 176, 221 |
| abstract_inverted_index.highlight | 259 |
| abstract_inverted_index.monitored | 131 |
| abstract_inverted_index.reduction | 204 |
| abstract_inverted_index.responses | 264 |
| abstract_inverted_index.severity. | 190 |
| abstract_inverted_index.subjected | 145 |
| abstract_inverted_index.symptoms. | 72 |
| abstract_inverted_index.targeting | 213 |
| abstract_inverted_index.treatment | 62, 196 |
| abstract_inverted_index.unchanged | 167, 177 |
| abstract_inverted_index.(SRT1720), | 41 |
| abstract_inverted_index.Contrarily | 191 |
| abstract_inverted_index.Objective: | 0 |
| abstract_inverted_index.Similarly, | 127 |
| abstract_inverted_index.activating | 39 |
| abstract_inverted_index.assessment | 102 |
| abstract_inverted_index.compounds, | 30 |
| abstract_inverted_index.mechanical | 105 |
| abstract_inverted_index.preventing | 66 |
| abstract_inverted_index.reflecting | 272 |
| abstract_inverted_index.regardless | 251 |
| abstract_inverted_index.researched | 268 |
| abstract_inverted_index.signaling. | 242 |
| abstract_inverted_index.structural | 161, 234 |
| abstract_inverted_index.treatment; | 229 |
| abstract_inverted_index.unaffected | 247 |
| abstract_inverted_index.understand | 58 |
| abstract_inverted_index.variations | 261, 277 |
| abstract_inverted_index.combination | 195, 228 |
| abstract_inverted_index.contributes | 10 |
| abstract_inverted_index.correlation | 187 |
| abstract_inverted_index.deposition. | 136 |
| abstract_inverted_index.development | 13 |
| abstract_inverted_index.effectively | 21 |
| abstract_inverted_index.mechanisms. | 281 |
| abstract_inverted_index.preclinical | 270 |
| abstract_inverted_index.progression | 70 |
| abstract_inverted_index.undetected, | 164 |
| abstract_inverted_index.17-month-old | 77 |
| abstract_inverted_index.Conclusions: | 211 |
| abstract_inverted_index.administered | 83 |
| abstract_inverted_index.combination. | 90 |
| abstract_inverted_index.improvements | 162 |
| abstract_inverted_index.corresponding | 165 |
| abstract_inverted_index.drug-response | 280 |
| abstract_inverted_index.heterogeneity | 275 |
| abstract_inverted_index.hyperalgesia, | 159 |
| abstract_inverted_index.hyperalgesia. | 106 |
| abstract_inverted_index.joint-related | 237 |
| abstract_inverted_index.treatment’s | 254 |
| abstract_inverted_index.Interestingly, | 243 |
| abstract_inverted_index.Lef1-dependent | 241 |
| abstract_inverted_index.administration | 27 |
| abstract_inverted_index.age-associated | 67 |
| abstract_inverted_index.effectiveness. | 255 |
| abstract_inverted_index.gender-related | 279 |
| abstract_inverted_index.osteoarthritis | 15 |
| abstract_inverted_index.post-traumatic | 147 |
| abstract_inverted_index.intra-articular | 25 |
| abstract_inverted_index.pathophysiology | 274 |
| abstract_inverted_index.histomorphometry | 96 |
| abstract_inverted_index.histopathological | 92 |
| abstract_inverted_index.post-traumatically | 44 |
| abstract_inverted_index.combination-treated | 154 |
| abstract_inverted_index.immunohistochemistry | 118 |
| cited_by_percentile_year.max | 95 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5028798804 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I197251160 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.75 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.65569313 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |