Site-specific characteristics of bone and progenitor cells in control and ovariectomized rats

Liu, Jie; Watanabe, Keiichiro; Dabdoub, Shareef M.; Lee, Beth S.; Kim, Do-Gyoon

Affiliations

¹Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA

²Division of Biostatistics and Computational Biology, Department of Periodontics, College of Dentistry and Dental Clinics, The University of Iowa, Iowa City, IA 52242, USA

³Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA

Abstract and keywords

One-third of postmenopausal women experience at least one osteoporotic bone fracture in their lifetime that occurs spontaneously or from low-impact events. However, osteoporosis-associated jaw bone fractures are extremely rare. It was also observed that jaw bone marrow stem cells (BMSCs) have a higher capacity to form mineralized tissues than limb BMSCs. At present, the underlying causes and mechanisms of variations between jaw bone and limb bone during postmenopause are largely unknown. Thus, the objective of the current study was to examine the site-specific effects of estrogen deficiency using comprehensive analysis of bone quantity and quality, and its association with characterization of cellular components of bone. Nine rats (female, 6 months old) for each bilateral sham and ovariectomy (OVX) surgery were obtained and maintained for 2 months after surgery. A hemi-mandible and a femur from each rat were characterized for parameters of volume, mineral density, cortical and trabecular morphology, and static and dynamic mechanical analysis. Another set of 5 rats (female, 9 months old) was obtained for assays of BMSCs. Following cytometry to identify BMSCs, bioassays for proliferation, and osteogenic, adipogenic, chondrogenic differentiation, and cell mitochondrial stress tests were performed. In addition, mRNA expression of BMSCs was analyzed. OVX decreased bone quantity and quality (mineral content, morphology, and energy dissipation) of femur while those of mandible were not influenced. Cellular assays demonstrated that mandible BMSCs showed greater differentiation than femur BMSCs. Gene ontology pathway analysis indicated that the mandibular BMSCs showed most significant differential expression of genes in the regulatory pathways of osteoblast differentiation, SMAD signaling, cartilage development, and glucose transmembrane transporter activity. These findings suggested that active mandibular BMSCs maintain bone formation and mineralization by balancing the rapid bone resorption caused by estrogen deficiency. These characteristics likely help reduce the risk of osteoporotic fracture in postmenopausal jawbone.

Keywords: Site-specific characteristics; OVX; Tissue mineral density; Dynamic mechanical analysis; Nanoindentation; Bone marrow stem cells

Links

DOI: 10.1016/j.bone.2022.116501

PubMed: 35872108

WoS: 000837142700001

History

Received: 2022-03-18

Revised: 2022-07-11

Accepted: 2022-07-18

Online: 2022-07-21

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