Lactation alters fluid flow and solute transport in maternal skeleton: A multiscale modeling study on the effects of microstructural changes and loading frequency.

The female skeleton undergoes significant material and ultrastructural changes to meet high calcium demands during reproduction and lactation. Through the peri-lacunar/canalicular remodeling (PLR), osteocytes actively resorb surrounding matrix and enlarge their lacunae and canaliculi during lactation, which are quickly reversed after weaning. How these changes alter the physicochemical environment of osteocytes, the most abundant and primary mechanosensing cells in bone, are not well understood.

Maternal bone adaptation to mechanical loading during pregnancy, lactation, and post-weaning recovery.

The maternal skeleton undergoes dramatic bone loss during pregnancy and lactation, and substantial bone recovery post-weaning. The structural adaptations of maternal bone during reproduction and lactation exert a better protection of the mechanical integrity at the critical load-bearing sites, suggesting the importance of physiological load-bearing in regulating reproduction-induced skeletal alterations. Although it is suggested that physical exercise during pregnancy and breastfeeding improves women's physical and psychological well-being, its effects on maternal bone health remain unclear.

Mechanical Regulation of the Maternal Skeleton during Reproduction and Lactation.

Purpose Of Review: This review summarizes recently published data on the effects of pregnancy and lactation on bone structure, mechanical properties, and mechano-responsiveness in an effort to elucidate how the balance between the structural and metabolic functions of the skeleton is achieved during these physiological processes.

Recent Findings: While pregnancy and lactation induce significant changes in bone density and structure to provide calcium for fetal/infant growth, the maternal physiology also comprises several innate compensatory mechanisms that allow for the maintenance of skeletal mechanical integrity. Both clinical and animal studies suggest that pregnancy and lactation lead to adaptations in cortical bone structure to allow for rapid calcium release from the trabecular compartment while maintaining whole bone stiffness and strength.

The dependences of osteocyte network on bone compartment, age, and disease.

Osteocytes, the most abundant bone cells, form an interconnected network in the lacunar-canalicular pore system (LCS) buried within the mineralized matrix, which allows osteocytes to obtain nutrients from the blood supply, sense external mechanical signals, and communicate among themselves and with other cells on bone surfaces. In this study, we examined key features of the LCS network including the topological parameter and the detailed structure of individual connections and their variations in cortical and cancellous compartments, at different ages, and in two disease conditions with altered mechanosensing (perlecan deficiency and diabetes). LCS network showed both topological stability, in terms of conservation of connectivity among osteocyte lacunae (similar to the "nodes" in a computer network), and considerable variability the pericellular annular fluid gap surrounding lacunae and canaliculi (similar to the "bandwidth" of individual links in a computer network).

Bone's responses to mechanical loading are impaired in type 1 diabetes.

Diabetes adversely impacts many organ systems including the skeleton. Clinical trials have revealed a startling elevation in fracture risk in diabetic patients. Bone fractures can be life threatening: nearly 1 in 6 hip fracture patients die within one year.

Imaging and quantifying solute transport across periosteum: implications for muscle-bone crosstalk.

Muscle and bone are known to act as a functional unit and communicate biochemically during tissue development and maintenance. Muscle-derived factors (myokines) have been found to affect bone functions in vitro. However, the transport times of myokines to penetrate into bone, a critical step required for local muscle-bone crosstalk, have not been quantified in situ or in vivo.

In situ intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading.

Osteocytes have been hypothesized to be the major mechanosensors in bone. How in situ osteocytes respond to mechanical stimuli is still unclear because of technical difficulties. In vitro studies have shown that osteocytes exhibited unique calcium (Ca(2+)) oscillations to fluid shear.

Perlecan-containing pericellular matrix regulates solute transport and mechanosensing within the osteocyte lacunar-canalicular system.

The pericellular matrix (PCM), a thin coating surrounding nearly all mammalian cells, plays a critical role in many cell-surface phenomena. In osteocytes, the PCM is believed to control both "outside-in" (mechanosensing) and "inside-out" (signaling molecule transport) processes. However, the osteocytic PCM is challenging to study in situ because it is thin (∼100 nm) and enclosed in mineralized matrix.

Functional characterization of normal and degraded bovine meniscus: rate-dependent indentation and friction studies.

The menisci are known to play important roles in normal joint function and the development of diseases such as osteoarthritis. However, our understanding of meniscus' load bearing and lubrication properties at the tissue level remains limited. The objective of this investigation was to characterize the site- and rate-dependency of the compressive and frictional responses of the meniscus under a spherical contact load.