Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis
Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This ov...
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The British Editorial Society of Bone & Joint Surgery
2025-03-01
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| Series: | Bone & Joint Research |
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| Online Access: | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.143.BJR-2024-0241.R1 |
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| author | Raquel Largo Aranzazu Mediero Cristina Villa-Gomez Ismael Bermejo-Alvarez Gabriel Herrero-Beaumont |
| author_facet | Raquel Largo Aranzazu Mediero Cristina Villa-Gomez Ismael Bermejo-Alvarez Gabriel Herrero-Beaumont |
| author_sort | Raquel Largo |
| collection | DOAJ |
| description | Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes’ anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease. Cite this article: Bone Joint Res 2025;14(3):199–207. |
| format | Article |
| id | doaj-art-e993bdd47a92449d8933dbec3470e0b3 |
| institution | Kabale University |
| issn | 2046-3758 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | The British Editorial Society of Bone & Joint Surgery |
| record_format | Article |
| series | Bone & Joint Research |
| spelling | doaj-art-e993bdd47a92449d8933dbec3470e0b32025-08-20T03:44:17ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582025-03-0114319920710.1302/2046-3758.143.BJR-2024-0241.R1Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritisRaquel Largo0https://orcid.org/0000-0001-6525-2944Aranzazu Mediero1https://orcid.org/0000-0002-5368-574XCristina Villa-Gomez2https://orcid.org/0000-0002-7520-1603Ismael Bermejo-Alvarez3https://orcid.org/0000-0003-2563-7908Gabriel Herrero-Beaumont4https://orcid.org/0000-0002-3241-991XJoint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, SpainJoint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, SpainJoint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, SpainJoint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, SpainJoint and Bone Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz UAM, Madrid, SpainOsteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes’ anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease. Cite this article: Bone Joint Res 2025;14(3):199–207.https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.143.BJR-2024-0241.R1osteoarthritismechanical overloadinginflammationaberrant anabolismtreatmentosteoarthritis (oa)chondrocytescartilage tissueosteoarthritic chondrocytesobesitypharmacotherapyarticular cartilagemechanical stressoverweightmetabolic syndrome |
| spellingShingle | Raquel Largo Aranzazu Mediero Cristina Villa-Gomez Ismael Bermejo-Alvarez Gabriel Herrero-Beaumont Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis Bone & Joint Research osteoarthritis mechanical overloading inflammation aberrant anabolism treatment osteoarthritis (oa) chondrocytes cartilage tissue osteoarthritic chondrocytes obesity pharmacotherapy articular cartilage mechanical stress overweight metabolic syndrome |
| title | Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis |
| title_full | Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis |
| title_fullStr | Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis |
| title_full_unstemmed | Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis |
| title_short | Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis |
| title_sort | aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis |
| topic | osteoarthritis mechanical overloading inflammation aberrant anabolism treatment osteoarthritis (oa) chondrocytes cartilage tissue osteoarthritic chondrocytes obesity pharmacotherapy articular cartilage mechanical stress overweight metabolic syndrome |
| url | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.143.BJR-2024-0241.R1 |
| work_keys_str_mv | AT raquellargo aberrantanabolismhindersconstructivemetabolismofchondrocytesbypharmacotherapyinosteoarthritis AT aranzazumediero aberrantanabolismhindersconstructivemetabolismofchondrocytesbypharmacotherapyinosteoarthritis AT cristinavillagomez aberrantanabolismhindersconstructivemetabolismofchondrocytesbypharmacotherapyinosteoarthritis AT ismaelbermejoalvarez aberrantanabolismhindersconstructivemetabolismofchondrocytesbypharmacotherapyinosteoarthritis AT gabrielherrerobeaumont aberrantanabolismhindersconstructivemetabolismofchondrocytesbypharmacotherapyinosteoarthritis |