Histomorphological Study And Biological Behavior Of Osteocytes In Senile And Postmenopausal Osteoporosis

Objectives: With the acceleration of population aging,some age-related chronic diseases caused by the natural degradation of physiological functions,such as osteoporosis and fractures,have become increasingly prominent and widely concerned.Aging and estrogen deficiency predispose to bone homeostasis imbalance,allowing bone resorption to be more than bone formation,resulting in decreased bone mass,poor bone structure and increased bone fragility,and eventually leading to osteoporosis and fractures.Osteocytes,the most abundant cells in mature bone tissue,can survive for decades in the bone matrix.Osteocytes connect with surrounding cells through dendrites,form a three-dimensional network in the bone,sense and transmit mechanical and chemical signals,participate in regulating the differentiation of osteoblasts and osteoclasts,and regulate the formation of adipose tissue in the bone marrow cavity,playing an important role in the maintenance of bone homeostasis.In addition,osteocyte apoptosis induces osteoclast precursor cell recruitment and subsequent bone resorption.Therefore,exploring the state of osteocytes in osteoporosis related to aging and estrogen deficiency is of great significance for the prevention and treatment of such diseases.This study explores the state of osteocytes in osteoporosis related to aging and estrogen deficiency by establishing a model of aging and estrogen deficiency,observes the changes of LCN and osteocyte apoptosis,and provides new ideas for the clinical prevention and treatment of osteoporosis and fragility fractures.Methods: A model of senile osteoporosis was established,and mouse femurs with PN5,1m,2m,3m,4m,8m,9m,12 m and 13 m were collected;A model of postmenopausal osteoporosis was established by removing mouse ovaries and mouse femurs were collected.By HE staining,static histomorphometric analyses were performed,including BA/TA,Tb.Th,Tb.N,Tb.Sp,N.Ob/BS,Ob.S/BS,N.OC/BS,and Oc.S/BS,and the percentage of empty lacunas was counted.By silver nitrate staining,the histomorphological changes of LCN were observed,including canalicular length,canalicular density,canalicular branching,canalicular connectivity,and lacuno-canalicular area/BA.By TUNEL staining,count the percentage of apoptotic cells.Count the percentage of HMGB1-positive cells by HMGB1 immunohistochemical staining.Results: 1.In the senile osteoporsis mouse model,bone mass loss and tubular density decreased at 4 months of age,the percentage of empty lacunas increased significantly at 8 months of age,the number and activity of osteoblasts decreased significantly and HMGB1 expression was significantly upregulated at 9 months of age,the number and activity of osteoclasts were significantly enhanced and apoptotic osteocytes increased significantly at 12 months of age.Osteocyte apoptosis was negatively correlated with bone mass and LCN integrity,strongly negatively correlated with the number of osteoblasts,and strongly positively correlated with HMGB1 expression.2.In the mouse model of postmenopausal osteoporosis,compared with the Sham group,the OVX group had osteopenia,increased number and activity of osteoclasts,increased percentage of empty lacunas,LCN damage,increased osteocyte apoptosis,and no significant difference in the number and activity of osteoblasts.Osteocyte apoptosis was negatively correlated with bone mass,positively correlated with osteoclast number and surface,and strongly positively correlated with HMGB1 expression.Conclusions: 1.Aging can lead to damage to LCN and apoptosis of osteocytes,which may be involved in regulating the activity of osteoblasts and osteoclasts by producing and releasing HMGB1,ultimately leading to bone loss.2.Estrogen deficiency can lead to damage to LCN and apoptosis of osteocytes,which may be involved in regulating osteoclast activity by producing and releasing HMGB1,ultimately leading to bone loss.