Buenzli PR, Sims NA. Quantifying the osteocyte network in the human skeleton. Bone. 2015;75:144–50.

Article  CAS  PubMed  Google Scholar 

Jansson JO, Palsdottir V, Hagg DA, Schele E, Dickson SL, Anesten F, et al. Body weight homeostat that regulates fat mass independently of leptin in rats and mice. Proc Natl Acad Sci U S A. 2018;115(2):427–32.

Article  CAS  PubMed  Google Scholar 

Jansson JO, Anesten F, Hagg D, Zlatkovic J, Dickson SL, Jansson PA, et al. The dual hypothesis of homeostatic body weight regulation, including gravity-dependent and leptin-dependent actions. Philos Trans R Soc Lond B Biol Sci. 1888;2023(378):20220219.

Google Scholar 

•• Baroi S, Czernik PJ, Chougule A, Griffin PR, Lecka-Czernik B. PPARG in osteocytes controls sclerostin expression, bone mass, marrow adiposity and mediates TZD-induced bone loss. Bone. 2021;147: 115913. This study showed for the first time that sclerostin is under transcriptional control of PPARG.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Kim SP, Seward AH, Garcia-Diaz J, Alekos N, Gould NR, Aja S, et al. Peroxisome proliferator activated receptor-gamma in osteoblasts controls bone formation and fat mass by regulating sclerostin expression. iScience. 2023;26(7):106999. This study linked sclerostin levels in circulation with "beiging" of extramedullary adipose tissue.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Chougule A, Baroi S, Czernik PJ, Crowe E, Chang MR, Griffin PR, et al. Osteocytes contribute via nuclear receptor PPAR-alpha to maintenance of bone and systemic energy metabolism. Front Endocrinol (Lausanne). 2023;14:1145467. This study discovered PPARA as a regulator of osteocyte secretome supporting bone marrow adipogenesis and "beiging" of extramedullary adipose tissue.

Article  PubMed  Google Scholar 

• Brun J, Berthou F, Trajkovski M, Maechler P, Foti M, Bonnet N. Bone regulates browning and energy metabolism through mature osteoblast/osteocyte PPARgamma expression. Diabetes. 2017;66(10):2541–54. This is the first study indicating that PPARG in osteocytes regulates adipose tissue and systemic energy metabolism.

Article  CAS  PubMed  Google Scholar 

Sato M, Asada N, Kawano Y, Wakahashi K, Minagawa K, Kawano H, et al. Osteocytes regulate primary lymphoid organs and fat metabolism. Cell Metab. 2013;18(5):749–58.

Article  CAS  PubMed  Google Scholar 

Ukita M, Yamaguchi T, Ohata N, Tamura M. Sclerostin enhances adipocyte differentiation in 3T3-L1 cells. J Cell Biochem. 2016;117(6):1419–28.

Article  CAS  PubMed  Google Scholar 

Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, et al. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005;309(5737):1074–8.

Article  CAS  PubMed  Google Scholar 

• Fairfield H, Falank C, Harris E, Demambro V, McDonald M, Pettitt JA, et al. The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis. J Cell Physiol. 2018;233(2):1156–67. This study provides in vitro and in vivo evidence for sclerostin role in support of bone marrow adipogenesis.

Article  CAS  PubMed  Google Scholar 

Kim SP, Frey JL, Li Z, Kushwaha P, Zoch ML, Tomlinson RE, et al. Sclerostin influences body composition by regulating catabolic and anabolic metabolism in adipocytes. Proc Natl Acad Sci U S A. 2017;114(52):E11238–47.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim SP, Da H, Wang L, Taketo MM, Wan M, Riddle RC. Bone-derived sclerostin and Wnt/beta-catenin signaling regulate PDGFRalpha(+) adipoprogenitor cell differentiation. FASEB J. 2021;35(11): e21957.

Article  CAS  PubMed  Google Scholar 

Frey JL, Li Z, Ellis JM, Zhang Q, Farber CR, Aja S, et al. Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast. Mol Cell Biol. 2015;35(11):1979–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fulzele K, Lai F, Dedic C, Saini V, Uda Y, Shi C, et al. Osteocyte-secreted Wnt signaling inhibitor sclerostin contributes to beige adipogenesis in peripheral fat depots. J Bone Miner Res. 2017;32(2):373–84.

Article  CAS  PubMed  Google Scholar 

Chen M, Feng HZ, Gupta D, Kelleher J, Dickerson KE, Wang J, et al. G(s)alpha deficiency in skeletal muscle leads to reduced muscle mass, fiber-type switching, and glucose intolerance without insulin resistance or deficiency. Am J Physiol Cell Physiol. 2009;296(4):C930–40.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma YH, Schwartz AV, Sigurdsson S, Hue TF, Lang TF, Harris TB, et al. Circulating sclerostin associated with vertebral bone marrow fat in older men but not women. J Clin Endocrinol Metab. 2014;99(12):E2584–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Courtalin M, Bertheaume N, Badr S, During A, Lombardo D, Deken V, et al. Relationships between circulating sclerostin, bone marrow adiposity, other adipose deposits and lean mass in post-menopausal women. Int J Mol Sci. 2023;24(6):5922.

Sheng Z, Tong D, Ou Y, Zhang H, Zhang Z, Li S, et al. Serum sclerostin levels were positively correlated with fat mass and bone mineral density in central south Chinese postmenopausal women. Clin Endocrinol (Oxf). 2012;76(6):797–801.

Article  CAS  PubMed  Google Scholar 

Urano T, Shiraki M, Ouchi Y, Inoue S. Association of circulating sclerostin levels with fat mass and metabolic disease–related markers in Japanese postmenopausal women. J Clin Endocrinol Metab. 2012;97(8):E1473–7.

Article  CAS  PubMed  Google Scholar 

Tozzi R, Masi D, Cipriani F, Contini S, Gangitano E, Spoltore ME, et al. Circulating SIRT1 and sclerostin correlates with bone status in young women with different degrees of adiposity. Nutrients. 2022;14(5):983.

Stechschulte LA, Czernik PJ, Rotter ZC, Tausif FN, Corzo CA, Marciano DP, et al. PPARG post-translational modifications regulate bone formation and bone resorption. EBioMedicine. 2016;10:174–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Baroi S, Czernik PJ, Khan MP, Letson J, Crowe E, Chougule A, et al. PPARG in osteocytes controls cell bioenergetics and systemic energy metabolism independently of sclerostin levels in circulation. bioRxiv. 2024. doi: https://doi.org/10.1101/2024.04.04.588029. This study showed that osteocyte bioenergetics under control of PPARG contribute significantly to the levels of systemic energy metabolism.

Farr JN, Kaur J, Doolittle ML, Khosla S. Osteocyte cellular senescence. Curr Osteoporos Rep. 2020;18(5):559–67.

Article  PubMed  PubMed Central  Google Scholar 

Farr JN, Xu M, Weivoda MM, Monroe DG, Fraser DG, Onken JL, et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat Med. 2017;23(9):1072–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019;571(7764):183–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24(8):1246–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2001;2(3):165–71.

Article  CAS  PubMed  Google Scholar 

Li Z, Hardij J, Bagchi DP, Scheller EL, MacDougald OA. Development, regulation, metabolism and function of bone marrow adipose tissues. Bone. 2018;110:134–40.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lecka-Czernik B, Rosen CJ, Kawai M. Skeletal aging and the adipocyte program: New insights from an “old” molecule. Cell Cycle. 2010;9(18):3648–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aaron N, Kraakman MJ, Zhou Q, Liu Q, Costa S, Yang J, et al. Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells. Elife. 2021;10:e69209.

Wiley CD, Sharma R, Davis SS, Lopez-Dominguez JA, Mitchell KP, Wiley S, et al. Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis. Cell Metab. 2021;33(6):1124-36 e5.

Article  CAS