Dataset Information

Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

ABSTRACT:

Objective

To investigate the role of Ca^2+/calmodulin-dependent protein kinase 2 (CaMKK2) in post-traumatic osteoarthritis (PTOA).

Methods

Destabilization of the medial meniscus (DMM) or sham surgeries were performed on 10-week-old male wild-type (WT) and Camkk2^-/- mice. Half of the DMM-WT mice and all other cohorts (n = 6/group) received tri-weekly intraperitoneal (i.p.) injections of saline whereas the remaining DMM-WT mice (n = 6/group) received i.p. injections of the CaMKK2 inhibitor STO-609 (0.033 mg/kg body weight) thrice a week. Study was terminated at 8- or 12-weeks post-surgery, and knee joints processed for microcomputed tomography imaging followed by histology and immunohistochemistry. Primary articular chondrocytes were isolated from knee joints of 4-6-day-old WT and Camkk2^-/- mice, and treated with 10 ng/ml interleukin-1β (IL)-1β for 24 or 48 h to investigate gene and protein expression.

Results

CaMKK2 levels and activity became elevated in articular chondrocytes following IL-1β treatment or DMM surgery. Inhibition or absence of CaMKK2 protected against DMM-associated destruction of the cartilage, subchondral bone alterations and synovial inflammation. When challenged with IL-1β, chondrocytes lacking CaMKK2 displayed attenuated inflammation, cartilage catabolism, and resistance to suppression of matrix synthesis. IL-1β-treated CaMKK2-null chondrocytes displayed decreased IL-6 production, activation of signal transducer and activator of transcription 3 (Stat3) and matrix metalloproteinase 13 (MMP13), indicating a potential mechanism for the regulation of inflammatory responses in chondrocytes by CaMKK2.

Conclusions

Our findings reveal a novel function for CaMKK2 in chondrocytes and highlight the potential for its inhibition as an innovative therapeutic strategy in the prevention of PTOA.

SUBMITTER: Mevel E

PROVIDER: S-EPMC8712369 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

Mével E E Shutter J A JA Ding X X Mattingly B T BT Williams J N JN Li Y Y Huls A A Kambrath A V AV Trippel S B SB Wagner D D Allen M R MR O'Keefe R R Thompson W R WR Burr D B DB Sankar U U

Osteoarthritis and cartilage 20210917 1

<h4>Objective</h4>To investigate the role of Ca<sup>2+/</sup>calmodulin-dependent protein kinase 2 (CaMKK2) in post-traumatic osteoarthritis (PTOA).<h4>Methods</h4>Destabilization of the medial meniscus (DMM) or sham surgeries were performed on 10-week-old male wild-type (WT) and Camkk2<sup>-/-</sup> mice. Half of the DMM-WT mice and all other cohorts (n = 6/group) received tri-weekly intraperitoneal (i.p.) injections of saline whereas the remaining DMM-WT mice (n = 6/group) received i.p. inject ...[more]

PMID: 34506942

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Dataset Information

Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

Objective

Methods

Results

Conclusions

Publications

Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

Similar Datasets

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