Jun Zhang1, Jaesuh Park1, Jung-Woo Lee2, Yong-Dae Kwon3, Eun-Cheol Kim4. 1. Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447, Republic of Korea. 2. Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447, South Korea. 3. Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447, South Korea. yongdae.kwon@gmail.com. 4. Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447, Republic of Korea. eckim@khu.ac.kr.
Abstract
OBJECTIVES: Although bisphosphonates (BPs) are known to be associated with osteonecrosis of the maxilla, the precise effects of BPs on bone metabolism in human maxillary sinus mucosal cells (HMSMCs) are not yet known. The purposes of this study were to examine the effects of the BPs zoledronate (ZOL) and alendronate (ALN) on osteoblastic and osteoclastic differentiation in HMSMCs and to investigate the signaling pathways involved. MATERIALS AND METHODS: The effects of ZOL and ALN were assessed for osteoblast differentiation by alkaline phosphatase (ALP) activity, alizarin red staining, and RT-PCR for genes encoding Runx2 and osterix. Receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs) was also examined. RESULTS: ZOL and ALN both suppressed osteoblastic differentiation, as evidenced by their effects on ALP activity, mineralization nodule formation, and the mRNA expression levels of osteoblastic transcript factors. The RANKL/osteoprotegerin ratio in HMSMCs was increased by ALN, whereas ZOL had the opposite effect. Conditioned medium obtained from ALN-treated HMSMCs stimulated osteoclast formation and upregulated NFATc1 expression, whereas conditioned medium from ZOL-treated cells did not. ALN was more cytotoxic and stimulated apoptosis more strongly than ZOL. BPs decreased the protein levels of the non-canonical Wnt signaling protein Wnt5a and calmodulin-dependent kinase II. Moreover, recombinant human Wnt5a reversed the effects of BPs on osteoblastic and osteoclastic differentiation. CONCLUSION: This study is the first demonstration that BPs exert negative effects on osteoblastic and osteoclastic processes via the non-canonical Wnt pathway in HMSMSCs. CLINICAL RELEVANCE: It suggests that patients taking BPs during the period of maxillary sinus lifting and amentation should be given special attention.
OBJECTIVES: Although bisphosphonates (BPs) are known to be associated with osteonecrosis of the maxilla, the precise effects of BPs on bone metabolism in human maxillary sinus mucosal cells (HMSMCs) are not yet known. The purposes of this study were to examine the effects of the BPszoledronate (ZOL) and alendronate (ALN) on osteoblastic and osteoclastic differentiation in HMSMCs and to investigate the signaling pathways involved. MATERIALS AND METHODS: The effects of ZOL and ALN were assessed for osteoblast differentiation by alkaline phosphatase (ALP) activity, alizarin red staining, and RT-PCR for genes encoding Runx2 and osterix. Receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs) was also examined. RESULTS:ZOL and ALN both suppressed osteoblastic differentiation, as evidenced by their effects on ALP activity, mineralization nodule formation, and the mRNA expression levels of osteoblastic transcript factors. The RANKL/osteoprotegerin ratio in HMSMCs was increased by ALN, whereas ZOL had the opposite effect. Conditioned medium obtained from ALN-treated HMSMCs stimulated osteoclast formation and upregulated NFATc1 expression, whereas conditioned medium from ZOL-treated cells did not. ALN was more cytotoxic and stimulated apoptosis more strongly than ZOL. BPs decreased the protein levels of the non-canonical Wnt signaling protein Wnt5a and calmodulin-dependent kinase II. Moreover, recombinant humanWnt5a reversed the effects of BPs on osteoblastic and osteoclastic differentiation. CONCLUSION: This study is the first demonstration that BPs exert negative effects on osteoblastic and osteoclastic processes via the non-canonical Wnt pathway in HMSMSCs. CLINICAL RELEVANCE: It suggests that patients taking BPs during the period of maxillary sinus lifting and amentation should be given special attention.
Authors: Poliana Mendes Duarte; Bruno César de Vasconcelos Gurgel; Antonio Wilson Sallum; Getúlio Rocha Nogueira Filho; Enilson Antonio Sallum; Francisco Humberto Nociti Journal: J Periodontol Date: 2005-01 Impact factor: 6.993
Authors: M F Moreau; C Guillet; P Massin; S Chevalier; H Gascan; M F Baslé; D Chappard Journal: Biochem Pharmacol Date: 2006-11-03 Impact factor: 5.858