OBJECTIVE: The non-neuronal cholinergic system represents non-neuronal cells that have the biochemical machinery to synthetize de novo and/or respond to acetylcholine (ACh). We undertook this study to investigate this biochemical machinery in chondrocytes and its involvement in osteoarthritis (OA). METHODS: Expression of the biochemical machinery for ACh metabolism and nicotinic ACh receptors (nAChR), particularly α7-nAChR, in human OA and murine chondrocytes was determined by polymerase chain reaction and ligand-binding. We investigated the messenger RNA expression of the human duplicate α7-nACh subunit, called CHRFAM7A, which is responsible for truncated α7-nAChR. We assessed the effect of nAChR on chondrocytes activated by interleukin-1β (IL-1β) and the involvement of α7-nAChR using chondrocytes from wild-type (WT) and α7-deficient Chrna7-/- mice. The role of α7-nAChR in OA was explored after medial meniscectomy in WT and Chrna7-/- mice. RESULTS: Human and murine chondrocytes express the biochemical partners of the non-neuronal cholinergic system and a functional α7-nAChR at their cell surface (n = 5 experiments with 5 samples each). The expression of CHRFAM7A in human OA chondrocytes (n = 23 samples) correlated positively with matrix metalloproteinase 3 (MMP-3) (r = 0.38, P < 0.05) and MMP-13 (r = 0.48, P < 0.05) expression. Nicotine decreased the IL-1β-induced IL-6 and MMP expression, in a dose-dependent manner, in WT chondrocytes but not in Chrna7-/- chondrocytes. Chrna7-/- mice that underwent meniscectomy (n = 7) displayed more severe OA cartilage damage (mean ± SD Osteoarthritis Research Society International [OARSI] score 4.46 ± 1.09) compared to WT mice that underwent meniscectomy (n = 9) (mean ± SD OARSI score 3.05 ± 0.9; P < 0.05). CONCLUSION: The non-neuronal cholinergic system is functionally expressed in chondrocytes. Stimulation of nAChR induces antiinflammatory and anticatabolic activity through α7-nAChR, but the anticatabolic activity may be mitigated by truncated α7-nAChR in human chondrocytes. In vivo experiments strongly suggest that α7-nAChR has a protective role in OA.
OBJECTIVE: The non-neuronal cholinergic system represents non-neuronal cells that have the biochemical machinery to synthetize de novo and/or respond to acetylcholine (ACh). We undertook this study to investigate this biochemical machinery in chondrocytes and its involvement in osteoarthritis (OA). METHODS: Expression of the biochemical machinery for ACh metabolism and nicotinic ACh receptors (nAChR), particularly α7-nAChR, in human OA and murine chondrocytes was determined by polymerase chain reaction and ligand-binding. We investigated the messenger RNA expression of the human duplicate α7-nACh subunit, called CHRFAM7A, which is responsible for truncated α7-nAChR. We assessed the effect of nAChR on chondrocytes activated by interleukin-1β (IL-1β) and the involvement of α7-nAChR using chondrocytes from wild-type (WT) and α7-deficient Chrna7-/- mice. The role of α7-nAChR in OA was explored after medial meniscectomy in WT and Chrna7-/- mice. RESULTS:Human and murine chondrocytes express the biochemical partners of the non-neuronal cholinergic system and a functional α7-nAChR at their cell surface (n = 5 experiments with 5 samples each). The expression of CHRFAM7A in human OA chondrocytes (n = 23 samples) correlated positively with matrix metalloproteinase 3 (MMP-3) (r = 0.38, P < 0.05) and MMP-13 (r = 0.48, P < 0.05) expression. Nicotine decreased the IL-1β-induced IL-6 and MMP expression, in a dose-dependent manner, in WT chondrocytes but not in Chrna7-/- chondrocytes. Chrna7-/- mice that underwent meniscectomy (n = 7) displayed more severe OA cartilage damage (mean ± SD Osteoarthritis Research Society International [OARSI] score 4.46 ± 1.09) compared to WT mice that underwent meniscectomy (n = 9) (mean ± SD OARSI score 3.05 ± 0.9; P < 0.05). CONCLUSION: The non-neuronal cholinergic system is functionally expressed in chondrocytes. Stimulation of nAChR induces antiinflammatory and anticatabolic activity through α7-nAChR, but the anticatabolic activity may be mitigated by truncated α7-nAChR in human chondrocytes. In vivo experiments strongly suggest that α7-nAChR has a protective role in OA.
Authors: Yuan Liu; Shi Xu; Haijun Zhang; Kaoliang Qian; Jiachen Huang; Xianger Gu; Yan Li; Yi Fan; Jun Hu Journal: Cell Death Dis Date: 2021-05-05 Impact factor: 8.469
Authors: Benjamin Terrier; Jérémie Sellam; Alice Courties; Jeremy Boussier; Jérôme Hadjadj; Nader Yatim; Laura Barnabei; Hélène Péré; David Veyer; Solen Kernéis; Nicolas Carlier; Frédéric Pène; Frédéric Rieux-Laucat; Bruno Charbit; Vincent Bondet; Darragh Duffy; Francis Berenbaum Journal: Sci Rep Date: 2021-06-04 Impact factor: 4.379
Authors: Mingzhu Gao; Chun Chen; Qiaoyan Zhang; Jun Bian; Luping Qin; Leilei Bao Journal: Evid Based Complement Alternat Med Date: 2021-09-30 Impact factor: 2.629