Msx-1 is suppressed in Bisphosphonate exposed jaw bone- analysis of bone turnover related cell signalling

Falk Wehrhan (1) , Peter Hyckel (2) , Kerstin Amann (3) , Jutta Ries (4) , Philipp Stockmann (4) , Karl Andreas Schlegel (4) , Friedrich Wilhelm Neukam (4) , Emeka Nkenke (4)

1 Oral and Maxillofacial Surgery
2 Department of Plastic Surgery/ St. Georg-hospital Eisenach
3 Institute of Pathology
4 Oral and Maxillofacial Surgery

Objectives: Bone-destructive disease treatments include bisphosphonates and antibodies against RANKL (aRANKL). Osteonecrosis of the jaw (ONJ) is a side effect. Etiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, BMP-2 and RANKL, in ONJ-affected and healthy jaw bone. Material and Methods: An automated immunohistochemistry based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n=20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results: Labeling indices were significantly lower for Msx-1 (p<0.03) and RANKL (p<0.003), and significantly higher (p<0.02) for BMP-2 in ONJ compared to healthy bone. Expression was 7-fold lower (p<0.03) for Msx-1, 22-fold lower (p<0.001) for RANKL, and 8-fold higher (p<0.02) for BMP-2 in ONJ bone. Conclusions: Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explaination of the exclusivity of ONJ in jaw bone. Functional analyzes of Msx-1- RANKL interaction during bone remodeling should be performed in the future.

Mots clés: Medicine

Falk Wehrhan, Peter Hyckel, Kerstin Amann, Jutta Ries, Philipp Stockmann, et al.. Msx-1 is suppressed in Bisphosphonate exposed jaw bone- analysis of bone turnover related cell signalling. Oral Diseases, 2011, 17 (4), pp.433. ⟨10.1111/j.1601-0825.2010.01778.x⟩. ⟨hal-00618503⟩