Essence of"Shen(Kidney)Controlling Bones":Conceptual Analysis Based on Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis

As a traditional concept of Chinese medicine（CM）, the theory of ＂Shen（Kidney） controlling bones＂ has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal（HPA） axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis： cells that comprise bone tissue（osteo-related cells） are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.

Kidney Tubular-Cell Secretion of Osteoblast Growth Factor Is Increased by Kaempferol:A Scientific Basis for "The Kidney Controlling the Bone" Theory of Chinese Medicine

Objective： To study, at the cytological level, the basic concept of Chinese medicine that “the Kidney （Shen） controls the bone”. Methods： Kaempferol was isolated form Rhizoma Drynariae （Gu Sui Bu, GSB） and at several concentrations was incubated with opossum kidney （OK） cells, osteoblasts （MC3T3 El） and human fibroblasts （HF） at cell concentrations of 2 x 104/mL. Opossum kidney cell-conditioned culture media with kaempferol at 70 nmol/L （70kaθOKM） and without kaempferol （oOKM） were used to stimulate MC3T3 E1 and HF proliferation. The bone morphological protein receptors I and Ⅱ （BMPR I and Ⅱ） in OK cells were identified by immune-fluorescence staining and Western blot analysis. Results： Kaempferol was found to increase OK cell growth （P〈0.05）, but alone did not promote MC3T3 E1 or HF cell proliferation. However, although OKM by itself increased MC3T3 E1 growth by 198% （P〈0.01）, the 70kaθOKM further increased the growth of these cells by an additional 127% （P〈0.01）. It indicates that the kidney cell generates a previously unknown osteoblast growth factor （OGF） and kaempferol increases kidney cell secretion of OGF. Neither of these media had any significant effect on HF growth. Kaempferol also was found to increase the level of the BMPR Ⅱ in OK cells. Conclusions： This lends strong support to the original idea that the Kidney has a significant influence over bone-formation, as suggested by some long-standing Chinese medical beliefs, kaempferol may also serve to stimulate kidney repair and indirectly stimulate bone formation.

Brain neural effects of the ’tonifying kidney and benefiting marrow’ method in the treatment of osteoporosis

In Traditional Chinese Medicine(TCM),the'tonifying kidney and benefiting marrow'(TKBM)method is based on the theory that kidney controls bones,while marrow moistens bones.There have been aboundant theoretical studies on kidney controlling bones since Huangdi's Internal Classics.Howev-er,there are too few ones about the marrow moistening the bones.Researchers generally use the tonifying kidney method instead of the TKBM method,which causes lack of a unified standard and theoretical basis in evaluating the TKBM method.Herein,we first proposed the hypothesis that deficiency of marrow sea causes osteoporosis.Next,we prove the scientific validity of this hypothesis from the side of the TCM theory on the relationship among kidney,bone and marrow sea physiologically and pathologically.Based on this,we find that the TCM theory provides theoretical basis for deficiency of marrow sea causing osteoporosis.On the other side,Western Medicine theory holds that(a)physiologically,the brain regulates the bone mass via three pathways:the neuro-osteogenic network,neuro-endocrine-bone network,and neuropeptide-bone network;(b)pathologically,brain impacts bone mass via three major passways including the regulation of the sympathetic nervous system,secreting hormones that directly act on bone cells and regulating the synthesis and secretion of hormones in the intermediary organs,and neuropeptides such as neuropeptide Y(NPY),substance P(SP),and calcitonin gene-related peptide(CGRP).Evidences involving estrogen deficiency,sympatheticotonia,or neuropeptides imbalance prove that brain-bone mass regulation plays an important role in the pathogenesis of osteoporosis.Finally,we find that kidney invigoration method can change the concentrations of central neurotransmitters of norepinephrine and glutamate to regulate neuro-osteogenic network,and promote the recovery of ovarian function and have an estrogen-like effect by regulating the hypothalamus-pituitary-ovarian axis,which thus influences bone metabolism without clinically significant estro-gen-like side effects,and regulate NPY,CGRP and SP involved in the bone metabolism.These further support our hypothesis by revealing the brain neural mechanism of the TCM kidney invigoration method for preventing and treating osteoporosis.In the future,neuroimaging techniques may be useful in exploring its neural effects and also aid in developing new strategies for treating osteoporosis.