Exercise has beneficial effects on metabolism and on tissues. The exercise-induced muscle factor β-aminoisobutyric acid (BAIBA) plays a critical role in the browning of white fat and in insulin ...resistance. Here we show another function for BAIBA, that of a bone-protective factor that prevents osteocyte cell death induced by reactive oxygen species (ROS). l-BAIBA was as or more protective than estrogen or N-acetyl cysteine, signaling through the Mas-Related G Protein-Coupled Receptor Type D (MRGPRD) to prevent the breakdown of mitochondria due to ROS. BAIBA supplied in drinking water prevented bone loss and loss of muscle function in the murine hindlimb unloading model, a model of osteocyte apoptosis. The protective effect of BAIBA was lost with age, not due to loss of the muscle capacity to produce BAIBA but likely to reduced Mrgprd expression with aging. This has implications for understanding the attenuated effect of exercise on bone with aging.
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•The muscle metabolite l-BAIBA protects osteocytes from ROS-induced cell death•l-BAIBA prevents mitochondrial breakdown in osteocytes•The effects of l-BAIBA are mediated via MRGPRD that decreases with aging•In vivo, l-BAIBA reduces bone and muscle loss resulting from immobilization
Kitase et al. show that the muscle-derived factor l-BAIBA signals through the MRGPRD to prevent osteocyte cell death induced by reactive oxygen species, a function lost with aging.
Osteoporosis is caused by increased bone resorption and decreased bone formation. Intermittent administration of a fragment of Parathyroid hormone (PTH) activates osteoblast-mediated bone formation ...and is used in patients with severe osteoporosis. However, the mechanisms by which PTH elicits its anabolic effect are not fully elucidated. Here we show that the absence of the homeodomain protein TG-interacting factor 1 (Tgif1) impairs osteoblast differentiation and activity, leading to a reduced bone formation. Deletion of Tgif1 in osteoblasts and osteocytes decreases bone resorption due to an increased secretion of Semaphorin 3E (Sema3E), an osteoclast-inhibiting factor. Tgif1 is a PTH target gene and PTH treatment failed to increase bone formation and bone mass in Tgif1-deficient mice. Thus, our study identifies Tgif1 as a novel regulator of bone remodeling and an essential component of the PTH anabolic action. These insights contribute to a better understanding of bone metabolism and the anabolic function of PTH.
Osteoporosis and sarcopenia are age-related musculoskeletal pathologies that often develop in parallel. Osteoporosis is characterized by a reduced bone mass and an increased fracture risk. Sarcopenia ...describes muscle wasting with an increasing risk of injuries due to falls. The medical treatment of both diseases costs billions in health care per year. With the impact on public health and economy, and considering the increasing life expectancy of populations, more efficient treatment regimens are sought. The biomechanical interaction between both tissues with muscle acting on bone is well established. Recently, both tissues were also determined as secretory endocrine organs affecting the function of one another. New exciting discoveries on this front are made each year, with novel signaling molecules being discovered and potential controversies being described. While this review does not claim completeness, it will summarize the current knowledge on both the biomechanical and the biochemical link between muscle and bone. The review will highlight the known secreted molecules by both tissues affecting the other and finish with an outlook on novel therapeutics that could emerge from these discoveries.
Osteophytes - bony outgrowths on joint structures - are found in healthy individuals but are specifically present in late osteoarthritis (OA). Osteophyte development and function is not well ...understood, yet biomechanical stimuli are thought to be critical. Bone adapts to mechanical forces via the cellular network of osteocytes. The involvement of osteocytes in osteophyte formation and maturation has not been unravelled. Forty-three osteophytes from tibias of 23 OA patients (65 ± 9 years) were analysed. The trabecular bone structure of osteophytes presented with fewer trabeculae of lower bone mineral density compared to subchondral bone. We identified 40% early stage and 60% late stage osteophytes that significantly differed in their trabecular bone characteristics. Osteophyte bone revealed a higher number of osteocytes and a lower number of empty osteocyte lacunae per bone area than the subchondral bone. We found that OA osteophytes consist of younger bone material comprised of woven and lamellar bone with the capacity to develop into a late stage osteophyte potentially via the involvement of the osteocyte network. Our analysis of OA osteophytes implies a transition from woven to lamellar bone as in physiological bone growth within a pathological joint. Therefore, osteophyte development and growth present a valuable research subject when aiming to investigate the osteogenic signalling cascade.
Within the mineralized bone, osteocytes form a multifunctional mechanosensitive network orchestrating bone remodelling. A preserved osteocyte population is a crucial determinant of bone quality. In ...human auditory ossicles, the early decrease in osteocyte numbers but maintained integrity remains an unexplained phenomenon that might serve for sound transmission from air to the labyrinth. Here we analysed the frequency, size and composition of osteocyte lacunae in the auditory ossicles of 22 individuals from early postnatal period to old age. Mineralization of the bone matrix was determined using backscattered electron imaging. No signs of bone remodelling were observed above the age of 1 year. We detected characteristics of early bone tissue aging, such as decrease in osteocytes, lower total lacunar density and lacunar area, as well as high matrix mineralization accompanied by distinct accumulation of micropetrotic lacunae and decreased indentation depths. The majority of these changes took place in the first months and years of life, while afterwards only minor reorganization was present. With osteocyte apoptosis potentially being a consequence of low mechanical stimuli, the early loss of osteocytes without initiation of bone remodelling indicates an adaptive response conserving the architecture of the auditory ossicles and ensuring stable sound transmission throughout life.
Objectives
With the higher risk of dental implant failure with type 2 diabetes mellitus (T2DM), there is a need to characterize the jaw bones in those individuals. The aim of this post mortem study ...was to compare jaw bone quality of individuals with T2DM to healthy controls.
Material and methods
Bone cores from the edentulous lower first molar region and the region of mandibular angle were collected from male individuals with T2DM (
n
= 10, 70.6 ± 4.5 years) and healthy controls (
n
= 11, 71.5 ± 3.8 years) during autopsy. Within the T2DM, a subgroup treated with oral antidiabetics (OAD) and one on insulin were identified. Bone quality assessment encompassed evaluation of bone microstructure, matrix composition, and cellular activity, using microcomputed tomography (micro-CT), quantitative backscattered electron imaging (qBEI), Raman spectroscopy, and bone histomorphometry.
Results
In the mandibular angle, T2DM showed 51% lower porosity of the lingual cortex (
p
= 0.004) and 21% higher trabecular thickness (
p
= 0.008) compared to control. More highly mineralized bone packets were found in the buccal cortex of the mandibular angle in insulin-treated compared to OAD-treated T2DM group (
p
= 0.034). In the molar region, we found higher heterogeneity of trabecular calcium content in T2DM insulin compared to controls (
p
= 0.015) and T2DM OAD (
p
= 0.019). T2DM was associated with lower osteocyte lacunar size in the trabecular bone of the molar region (vs. control
p
= 0.03).
Conclusions
Alterations in microstructure, mineralization, and osteocyte morphology were determined in jaw bone of individuals with T2DM compared to controls.
Clinical relevance
Future studies will have to verify if the mild changes determined in this study will translate to potential contraindications for dental implant placements.
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