|
| Year/Study | Model used | Drug | Outcome |
|
| Törnkvist et al., 1984 [56] | Chicken mesenchymal limb-bud cells | Indomethacin (25–100 μM) | (i) No effect on osteogenesis and chondrogenesis |
|
| Ho et al., 1999 [57] | Osteoblasts derived from fetal rat calvaria | Ketorolac (0.1–1000 μM), Indomethacin (0.01–100 μM) | (i) All concentration of Ketorolac inhibited proliferation at 24 hours
(ii) 0.1 μM of indomethacin or higher inhibited proliferation
(iii) A dose dependant increase of ALP was found for concentration between 0.1–100 μM of Ketorolac
(iv) Both NSAIDs stimulated collagen type I synthesis |
|
|
Evans and Butcher,2004 [58] | Human trabecular bone osteoblasts | Indomethacin (0.003–0.3 μM/L) | (i) Inhibition of proliferation and increase in collagen synthesis and ALP in a dose dependant manner |
|
| Wang et al., 2004 [59] | MG63 human osteoblasts | Celecoxib (1–120 μM) | (i) Dose dependant decrease of cellular proliferation and stimulation of Ca++ production |
|
| Chang et al., 2005 [60] | Osteoblasts derived from fetal rat calvaria | Diclofenac, piroxicam, indomethacin Ketorolac (0.001–0.1 μM) | (i) All NSAIDs resulted in cell cycle arrest and cell death
(ii) Piroxicam had the least effect to produce osteoblastic dysfunction |
|
| Wang et al., 2006 [61] | BM-derived Rat MSCs | Aspirin 1, 5, 10 mmol/L | (i) Inhibition of MSCs proliferation |
|
| Wiontzek et al., 2006 [62] | MG63 human osteoblasts | Celecoxib (10 μM) | (i) No effect on Ca++ production, COX-2 expression, ALP and osteocalcin |
|
| Wolfesberger et al., 2006 [63] | Canine Osteosarcoma cell line | Meloxicam (1–200 μg/mL) | (i) Marked untiproliferative effect for concentrations over 100 while lower concentrations resulted in an increase of cell numbers |
|
| Chang et al., 2007 [64] | Human MSCs and D1-cells (Mice) | Indomethacin (10, 100 μM), Celecoxib (1, 10 μM) | (i) Inhibition of proliferation for both NSAIDs but no significant cytotoxic effect
(ii) Replenishment of PGE-1, PGE-2 and PGF2a did not reverse this negative effect |
|
| Kellinsalmi et al., 2007 [65] | Human MSCs | Indomethacin (1, 10, 100 μM), Parecoxib (1, 10, 100 μM),
NS398 (0.03, 0.3, 3 μM) | (i) All studied NSAIDs inhibited osteoblastic and osteoclastic differentiation
(ii) Significant increase of adipocytes suggesting diversion to adipogenesis instead of osteogenesis |
|
| Arpornmaeklong et al., 2008 [66] | Mouse calvaria cell line MC3T3-E1 | Indomethacin (0.1 μM), Celecoxib (1.5, 3, 9 μM) | (i) Inhibition of growth with both NSAIDs
(ii) Indomethacin had a higher inhibitory effect than Celecoxib |
|
| Abukawa et al., 2009 [67] | Porcine BM progenitor cells | Ibuprofen (0.1, 1, 3 mmol/L) | (i) 0.1 mmol/L had no effect on proliferation, ALP, bone matrix mineralization while inhibition found for the higher studied concentrations |
|
| Chang et al., 2009 [68] | Human osteoblasts | Indomethacin (0.1–1 μM),
Ketorolac (0.1–1 μM),
Piroxicam (0.1–1 μM),
Diclofenac (0.1–1 μM),
Celecoxib (1–10 μM) | (i) Inhibition of proliferation occurred with all studied NSAIDs
(ii) Replenishment of PGE-1, PGE-2 and PGF2a did not reverse this negative effect |
|
| Kolar et al., 2009 [69] | MG63 human osteoblasts | Celecoxib (2, 10, 50 μM) | (i) Marginal effect with the concentrations of 2 and 10 μM but 50 μM reduced cell viability and OPG secretion and stimulated oxygen consumption and GLUT-1 expression |
|
| Yoon et al., 2010 [70] | Human BM MSCs | Celecoxib (10, 20, 40 μM ), Naproxen (100, 200, 300 μM) | (i) No effect on ALP and Calcium content in absence of Interleukin 1β while in its presence ALP and Calcium was reduced only with the highest studied concentration |
|
| Guez et al., 2011 [71] | Human MG-63 Osteosarcoma Cell | Indomethacin (1–10 μM) Nimesulide (1–10 μM) Diclofenac (1–10 μM) | (i) All NSAIDs had an inhibiting effect on osteoblastic proliferation and significant effects on the antigenic profile
(ii) No treatment altered osteocalcin synthesis |
|
| Müller et al., 2011 [72] | Equine BM MSCs | Flunixin (10–1000 μM), phenylbutazone (10–1000 μM), Meloxicam (0.01–200 μM), Celecoxib (0.01–200 μM) | (i) Low NSAIDs concentrations had positive effect on proliferation while the higher ones inhibited proliferation
(ii) Adipogenic and chondrogenic differentiation was found unaltered however osteogenesis was significantly disrupted |
|
| Pountos et al., 2011 [73] | BM and TB derived MSCs | Diclofenac, Ketorolac, Parecoxib, Ketoprofen, Piroxicam, Meloxicam and Lornoxicam
(all 0.001 to 100 μg/mL) | (i) No effect on MSCs proliferation when cellular medium was supplemented with expected plasma concentrations
(ii) Negative effect encountered when high concentrations used (over 100 μg/mL)
(iii) NSAIDs in plasma concentrations had no effect on osteogenesis
(iv) Chondrogenesis was found inhibited by NSAIDs |
|
