Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing

Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain unclear.In this study,we revealed that macrophages in calluses secrete prosenescent factors,including grancalcin(GCA),during aging,which triggers SSPC senescence and impairs fracture healing.Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair.Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence.Mechanistically,GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction,resulting in cellular senescence.Depletion of Plxnb2 in SSPCs impaired fracture healing.Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice.Thus,our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence,and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Prevalence of Nontraumatic Osteonecrosis of the Femoral Head and its Associated Risk Factors in the Chinese Population： Results from a Nationally Representative Survey

Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.