Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (1): 212-219.DOI: 10.19852/j.cnki.jtcm.20230904.006
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REN Ping1, WANG Quanwu2, BAI Wei3, SUN Miao4, LIU Zheling5, GAO Ming5, WANG Liang5, PENG Bo5, XU Liguang3()
Received:
2022-11-11
Accepted:
2023-04-08
Online:
2024-02-15
Published:
2023-09-04
Contact:
XU Liguang, Department of Acupuncture, the affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, China. 33483857@qq.com. Telephone: +86-431-86177039
REN Ping, WANG Quanwu, BAI Wei, SUN Miao, LIU Zheling, GAO Ming, WANG Liang, PENG Bo, XU Liguang. Identifying the effective combination of acupuncture and traditional Chinese medicinal herbs for postmenopausal osteoporosis therapy through studies of their molecular regulation of bone homeostasis[J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 212-219.
Figure 1 Molecular regulation of osteoclast targets by drugs, hormones, and cytokines The schematic illustration showing various molecular targets in osteoclasts that are regulated by drugs, hormones and cytokines. Osteoblast produced RANKL stimulates and 17β-E2 or SERMs inhibits the fusion of MNC in the blood that are precursor cells for the formation of osteoclasts. RANKL is a pro-survival factor for mature osteoclasts whereas E2 or SERM induces their apoptosis. Denosumab by depriving osteoclasts of RANKL induces osteoclast apoptosis. N-BPs by inhibiting protein prenylation inhibit the cytoskeleton formation of osteoclasts which is necessary for their adherence to bone surface for resorption. Cathepsin K, a cysteine protease and the major collagenase produced by mature osteoclasts is secreted to the resorption site and degrades bone matrix by digesting type I collagen. RANKL: receptor-activator of nuclear kappaB ligand; MNC: mononuclear cells; N-BPs: nitrogen-containing bisphosphonates; 17β-E2: estradiol; SERM: selective estrogen receptor modulators (raloxifene); FPP: farnesyl pyrophosphate synthase. Refer to table 1 for possible intervention points by acupuncture and Traditional Chinese Medicine discussed in the text.
Figure 2 Molecular targets in osteoblasts regulated by drugs and hormones The schematic illustration showing various molecular targets in osteoblasts that are regulated by drugs and hormones. The bone anabolic drugs TPTD or ABL via the PTHR1 activates Wnt signaling by increasing the production of Wnt agonists Wnt3a and Wnt10B. Activation of Wnt pathway elicits a nuclear event which via the transcription factor TCF/LEF upregulates transcription of osteogenic genes (Runx2 and Col1). TPTD or ABL on the other hand upregulates the production of RANKL. E2 or SERMs via the cognate ERs downregulate the transcription of RANKL and vitamin D via the VDR upregulates OPG. Denosumab, the neutralizing antibody against the secreted RANKL suppresses RANKL action by neutralizing this osteoclastogenic cytokine. Green arrow: upregulation; red arrow: downregulation. TPTD: teriparatide (1-34 PTH); ABL: abaloparatide (1-36 PTHrP); TCF/LEF: T-cell factor/lymphoid enhancer factor; Col 1: type I collagen; Runx2: runt-related transcription factor 2; OPG: osteoprotegerin (decoy receptor of RANKL); FZD: frizzled receptor (Wnt receptor); LRP: low-density lipoprotein receptor-related protein (Wnt co-receptor). Refer to Table 1 for possible intervention points by acupuncture and Traditional Chinese Medicine discussed in the text.
Treatment type | Wnt pathway | /receptor activator of NF-KB ligand/osteoprotegerin ratio | Serum Estradiol levels | Cathepsin K |
---|---|---|---|---|
Acupuncture | Stimulates Wnt 3a | Suppresses the ratio | Increases | - |
Yinyanghuo (Herba Epimedii Brevicornus) | - | Suppresses the ratio | Increases | - |
Guanzhong (Rhizoma Dryopteridis Crassirhizomatis) | Stimulates Wnt 3a | Suppresses the ratio | - | - |
Danshen (Radix Salviae Miltiorrhizae) | - | Suppresses the ratio | - | Suppresses expression and function |
Table 1 Differential molecular targets of acupuncture and Traditional Chinese Medicine used in postmenopausal women concerning their skeletal effects
Treatment type | Wnt pathway | /receptor activator of NF-KB ligand/osteoprotegerin ratio | Serum Estradiol levels | Cathepsin K |
---|---|---|---|---|
Acupuncture | Stimulates Wnt 3a | Suppresses the ratio | Increases | - |
Yinyanghuo (Herba Epimedii Brevicornus) | - | Suppresses the ratio | Increases | - |
Guanzhong (Rhizoma Dryopteridis Crassirhizomatis) | Stimulates Wnt 3a | Suppresses the ratio | - | - |
Danshen (Radix Salviae Miltiorrhizae) | - | Suppresses the ratio | - | Suppresses expression and function |
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