Dataset Information

Intra-articular Administration of Triamcinolone Acetonide in a Murine Cartilage Defect Model Reduces Inflammation but Inhibits Endogenous Cartilage Repair.

ABSTRACT:

Background

Cartilage defects result in joint inflammation. The presence of proinflammatory factors has been described to negatively affect cartilage formation.

Purpose

To evaluate the effect and timing of administration of triamcinolone acetonide (TAA), an anti-inflammatory drug, on cartilage repair using a mouse model.

Study design

Controlled laboratory study.

Methods

A full-thickness cartilage defect was created in the trochlear groove of 10-week-old male DBA/1 mice (N = 80). Mice received an intra-articular injection of TAA or saline on day 1 or 7 after induction of the defect. Mice were euthanized on days 10 and 28 for histological evaluation of cartilage defect repair, synovial inflammation, and synovial membrane thickness.

Results

Mice injected with TAA had significantly less synovial inflammation at day 10 than saline-injected mice independent of the time of administration. At day 28, the levels of synovitis dropped toward healthy levels; nevertheless, the synovial membrane was thinner in TAA- than in saline-injected mice, reaching statistical significance in animals injected on day 1 (70.1 ± 31.9 µm vs 111.9 ± 30.9 µm, respectively; P = .01) but not in animals injected on day 7 (68.2 ± 21.86 µm vs 90.2 ± 21.29 µm, respectively; P = .26). A thinner synovial membrane was moderately associated with less filling of the defect after 10 and 28 days (r = 0.42, P = .02; r = 0.47, P = .01, respectively). Whereas 10 days after surgery there was no difference in the area of the defect filled and the cell density in the defect area between saline- and TAA-injected knees, filling of the defect at day 28 was lower in TAA- than in saline-injected knees for both injection time points (day 1 injection, P = .04; day 7 injection, P = .01). Moreover, there was less collagen type 2 staining in the filled defect area in TAA- than in saline-injected knees after 28 days, reaching statistical significance in day 1-injected knees (2.6% vs 18.5%, respectively; P = .01) but not in day 7-injected knees (7.4% vs 15.8%, respectively; P = .27).

Conclusion

Intra-articular injection of TAA reduced synovial inflammation but negatively affected cartilage repair. This implies that inhibition of inflammation may inhibit cartilage repair or that TAA has a direct negative effect on cartilage formation.

Clinical relevance

Our findings show that TAA can inhibit cartilage defect repair. Therefore, we suggest not using TAA to reduce inflammation in a cartilage repair setting.

SUBMITTER: Wesdorp MA

PROVIDER: S-EPMC9069659 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intra-articular Administration of Triamcinolone Acetonide in a Murine Cartilage Defect Model Reduces Inflammation but Inhibits Endogenous Cartilage Repair.

Wesdorp Marinus A MA Capar Serdar S Bastiaansen-Jenniskens Yvonne M YM Kops Nicole N Creemers Laura B LB Verhaar Jan A N JAN Van Osch Gerjo J V M GJVM Wei Wu W

The American journal of sports medicine 20220322 6

<h4>Background</h4>Cartilage defects result in joint inflammation. The presence of proinflammatory factors has been described to negatively affect cartilage formation.<h4>Purpose</h4>To evaluate the effect and timing of administration of triamcinolone acetonide (TAA), an anti-inflammatory drug, on cartilage repair using a mouse model.<h4>Study design</h4>Controlled laboratory study.<h4>Methods</h4>A full-thickness cartilage defect was created in the trochlear groove of 10-week-old male DBA/1 mic ...[more]

PMID: 35315287

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Project description:ObjectiveWhile the effect of triamcinolone acetonide extended-release (TA-ER) on reducing knee osteoarthritis (OA) pain has been reported, the effects on physical performance are incompletely understood. This open label clinical trial systematically evaluated the effects of intra-articular TA-ER on physical performance, self-reported function, and quality of life in participants with bilateral symptomatic knee OA 6, 12 (primary) and 24 weeks following bilateral injection of TA-ER (32 mg).MethodsSeventy participants were enrolled (61.4% women; age 64.0 ± 11.7; BMI 31.8 ± 5.7 kg/m2). Physical performance was measured by 30-s chair stand test, 40 m fast paced walk test (FPWT), and stair negotiation test at baseline and each follow-up visit. Physical function and quality of life (QOL) were measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS-PS) and pain was measured with numeric rating scale (NRS).ResultsIn comparison with baseline, self-reported pain, function, and quality of life were improved at each follow-up through 24 weeks and the number of chair-stands significantly improved following treatment by (mean ± SE) 1.9 ± 0.6 at 6-week (p = 0.0048) and by 1.8 ± 0.5 at 12-week follow-up (p = 0.0011) but was not statistically significant at 24-week follow-up (0.6 ± 0.6; p = 0.4711). Stair negotiation times were 7.2 ± 3.7, 7.1 ± 3.8, and 5.4 ± 4.0 s lower at the three respective follow-up timepoints, although these changes did not reach statistical significance (p = 0.0530, p = 0.0599, and p = 0.1793 respectively). The 40m-FPWT time did not significantly improve.ConclusionThese data indicate improvement in chair stand performance through 12 weeks post-injection and sustained improvement in participant-reported physical function through 24-week follow-up in adults with bilateral painful knee OA treated with TA-ER.

Project description:IntroductionSingle intra-articular (IA) injections of poly(lactic-co-glycolic acid) (PLGA) microsphere-based triamcinolone acetonide extended-release (TA-ER; formerly FX006) demonstrated sustained, clinically relevant benefits in patients with knee osteoarthritis. The local effects of TA-ER were assessed in normal canine knees in three nonclinical studies.MethodsKnees were evaluated for up to 6 weeks or 9 months after a single injection of TA-ER (2.1/6.25/18.75 mg TA), or TA crystalline suspension (TAcs, 18.75 mg TA), and for up to 6 months after three injections (every 1 or 3 months) of TA-ER (6.25/18.75 mg TA) or TAcs (18.75 mg). Vehicle-diluent, blank microspheres, and untreated knees were used as controls. Plasma and synovial fluid (SF) TA concentrations and standard histopathological assessment of the synovium were conducted. Articular cartilage morphology was assessed via modified Mankin scoring.ResultsPlasma and SF concentrations indicated prolonged dose-dependent TA joint residency with TA-ER compared with TAcs. Effects in articular cartilage were dose- and time-dependent and consistent with known effects of corticosteroids in the normal knee. Loss of Safranin O staining occurred, indicative of a reduction in cartilage matrix proteoglycan, and recovered in a similar manner for TA-ER and TAcs across all studies. Structural lesions were infrequent and generally comparable in severity between TA-ER and TAcs but slightly higher in incidence for TA-ER. Focal/multifocal foreign-body responses (FBR) to PLGA were observed in the superficial layer of the synovium, peaking after 4-6 weeks, with significant recovery or complete resolution by month 6.ConclusionsThese findings suggest that the effects of IA injections of TA-ER on cartilage are predominantly transient, and comparable to those observed with TAcs in the normal canine knee joint. These mild effects in the normal joint differ from the beneficial effects observed with TA-ER and other corticosteroids in disease models. The synovial FBR to PLGA microspheres was focal and transient.FundingFlexion Therapeutics, Inc. Plain language summary available for this article.

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Dataset Information

Intra-articular Administration of Triamcinolone Acetonide in a Murine Cartilage Defect Model Reduces Inflammation but Inhibits Endogenous Cartilage Repair.

Background

Purpose

Study design

Methods

Results

Conclusion

Clinical relevance

Publications

Intra-articular Administration of Triamcinolone Acetonide in a Murine Cartilage Defect Model Reduces Inflammation but Inhibits Endogenous Cartilage Repair.

Similar Datasets

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