51. Risedronate directly inhibits osteoclast differentiation and inflammatory bone loss
- Author
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Kwon Ha Yoon, Joung-Kyue Han, Jeung Woo Kim, Kwang-Jin Kim, Seon Kwan Juhng, Gi Youn Hong, Byoung Hyun Park, Hae Joong Cho, Chul Hong Chun, Ji Myung Bae, Yong-Il Shin, Jong Yun Kim, Min-Kye Choi, Han Bok Kwak, Kwang Mee Kim, Myeung Su Lee, Hun Soo Kim, Jeong-Joong Kim, and Jaemin Oh
- Subjects
musculoskeletal diseases ,Lipopolysaccharides ,medicine.medical_specialty ,Cell Survival ,medicine.medical_treatment ,Osteoporosis ,Pharmaceutical Science ,Osteoclasts ,Inflammation ,Bone tissue ,p38 Mitogen-Activated Protein Kinases ,Cell Line ,Mice ,Osteoclast ,Internal medicine ,medicine ,Animals ,Humans ,Bone Resorption ,Phosphorylation ,Pharmacology ,Mice, Inbred ICR ,biology ,Bone Density Conservation Agents ,NFATC Transcription Factors ,Chemistry ,Macrophages ,RANK Ligand ,Cell Differentiation ,Etidronic Acid ,General Medicine ,Bisphosphonate ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,RANKL ,Risedronic acid ,biology.protein ,Bone marrow ,medicine.symptom ,Proto-Oncogene Proteins c-fos ,Risedronic Acid ,medicine.drug - Abstract
Risedronate, a nitrogen-containing bisphosphonate, is widely used in the clinical field for the treatment of osteoporosis. Risedronate is known to exert its effects through binding to hydroxyapatite in bone tissue, inhibiting osteoclastic activity, and inducing apoptosis of osteoclasts. The purpose of this study was to determine the effects of risedronate on osteoclast differentiation in vitro and on an inflammatory bone loss model in vivo. Risedronate inhibited osteoclast differentiation in co-culture of bone marrow cells (BMCs) and osteoblasts, and suppressed receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-mediated osteoclast differentiation from bone marrow-derived macrophages (BMMs) in a dose-dependent manner without toxicity. Risedronate significantly inhibited expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 induced by RANKL. To examine the effect of risedronate on bone loss in vivo, we used a mouse model of lipopolysaccharide (LPS)-mediated bone loss. Micro-CT analysis of the femurs showed that LPS treatment caused bone loss. However, bone loss was significantly attenuated in mice administered with risedronate. Taken together, we conclude that risedronate exerts beneficial effects on osteoporosis by inhibiting osteoclast differentiation both directly and indirectly. In infectious conditions, the inhibitory effect of risedronate on bone erosion was excellent. Thus risedronate could be a treatment option for osteoporosis caused by inflammatory and infectious conditions.
- Published
- 2009