A Na+/K+ ATPase Pump Regulates Chondrocyte Differentiation and Bone Length Variation in Mice

The genetic and developmental mechanisms involved in limb formation are relatively well documented, but how these mechanisms are modulated by changes in chondrocyte physiology to produce differences in limb bone length remains unclear. Here, we used high throughput RNA sequencing (RNAseq) to probe the developmental genetic basis of variation in limb bone length in Longshanks, a mouse model of experimental evolution. We find that increased tibia length in Longshanks is associated with altered expression of a few key endochondral ossification genes such as Npr3, Dlk1, Sox9, and Sfrp1, as well reduced expression of Fxyd2, a facultative subunit of the cell membrane-bound Na+/K+ ATPase pump (NKA). Next, using murine tibia and cell cultures, we show a dynamic role for NKA in chondrocyte differentiation and in bone length regulation. Specifically, we show that pharmacological inhibition of NKA disrupts chondrocyte differentiation, by upregulating expression of mesenchymal stem cell markers (Prrx1, Serpina3n), downregulation of chondrogenesis marker Sox9, and altered expression of extracellular matrix genes (e.g., collagens) associated with proliferative and hypertrophic chondrocytes. Together, Longshanks and in vitro data suggest a broader developmental and evolutionary role of NKA in regulating limb length diversity.

Efficacy Comparison of Trifocal Bone Transport Using Unilateral External Fixator for Femoral and Tibial Bone Defects Caused by Infection

Background: This study aimed to evaluate the clinical and functional outcomes of patients with critical femoral and tibial bone defects treated by trifocal bone transport using the Ilizarov method.Methods: In a retrospective comparative study, 39 patients treated for lower limb bone non-union with bone loss measuring between 6 and 14 cm were included. Depending on the location of bone transport, the patients were divided into the femur group (n =18) and tibia groups (n =21). The demographics data, intraoperative records, and postoperative outcomes were documented and compared between the two groups. At the last follow-up, the bone and functional outcomes were evaluated according to the criterion given by the Association for the Study and Application of the Method of the Ilizarov (ASAMI) and postoperative complications evaluated by Paley classification.Results: The average follow-up time was 26.1 months (range 17–34 months) since the unilateral external fixators were removed. The mean size of the bone defect was 8.3 cm in the femur group, and 7.5 cm in the tibia group. All bone defects were reconstructed successfully. The mean time in external fixation in the femur group was 334.4 days, and in the tibia group was 344.6 days. The external fixation index (EFI) measured 55.9 days/cm in the femur group and 65 days/cm in the tibia group. A statistically significant difference of bone grade was found between the two groups (excellent/good/fair/poor, 3/11/3/1 vs 2/13/4/2, P<0.05), as well as the function grade in two groups (excellent/good/fair/poor/failure, 3/14/1/0 vs 4/13/3/1, P<0.05). According to the ASAMI classification, the clinical and functional results in the femur group were better than in the tibia group. The complication rate of the two groups was 94.4% vs 76.2% (femur vs tibia). One femur and five tibias were performed additional surgery because of delayed union and axial deviation. Conclusions: The trifocal bone transport using the unilateral external fixator is a reliable treatment in the management of post-traumatic and post-infection lower limb bone defects (>6cm). In the comparison of the tibia, the trifocal bone transport treatment period of the femur was shorter, the functional recovery was better and the risk of minor complications was higher.

ARMA-Based Segmentation of Human Limb Motion Sequences

With the development of human motion capture (MoCap) equipment and motion analysis technologies, MoCap systems have been widely applied in many fields, including biomedicine, computer vision, virtual reality, etc. With the rapid increase in MoCap data collection in different scenarios and applications, effective segmentation of MoCap data is becoming a crucial issue for further human motion posture and behavior analysis, which requires both robustness and computation efficiency in the algorithm design. In this paper, we propose an unsupervised segmentation algorithm based on limb-bone partition angle body structural representation and autoregressive moving average (ARMA) model fitting. The collected MoCap data were converted into the angle sequence formed by the human limb-bone partition segment and the central spine segment. The limb angle sequences are matched by the ARMA model, and the segmentation points of the limb angle sequences are distinguished by analyzing the good of fitness of the ARMA model. A medial filtering algorithm is proposed to ensemble the segmentation results from individual limb motion sequences. A set of MoCap measurements were also conducted to evaluate the algorithm including typical body motions collected from subjects of different heights, and were labeled by manual segmentation. The proposed algorithm is compared with the principle component analysis (PCA), K-means clustering algorithm (K-means), and back propagation (BP) neural-network-based segmentation algorithms, which shows higher segmentation accuracy due to a more semantic description of human motions by limb-bone partition angles. The results highlight the efficiency and performance of the proposed algorithm, and reveals the potentials of this segmentation model on analyzing inter- and intra-motion sequence distinguishing.

БИЛАТЕРАЛЬНАЯ АСИММЕТРИЯ ДЛИННЫХ КОСТЕЙ СКЕЛЕТА У ТОБОЛО-ИРТЫШСКИХ ТАТАР

В статье представлены результаты изучения билатеральной асимметрии длинных костей скелета у четырёх групп тоболо-иртышских татар: аялынских, тобольских, тюменских и коурдакско-саргатских татар. Для каждой группы мужчин и женщин была рассчитаны коэффициенты асимметрии (использовалась формула R–L), процентное соотношение которых показывает, что наиболее симметричная скелетная система у аялынских татар, а самая асимметричная у коурдакско-саргатских татар. При анализе коэффициентов асимметрии отдельных костей, было выявлено, что во всех исследуемых группах у мужчин и женщин самой асимметричной костью является плечевая кость. Анализ коэффициентов асимметрии по отдельным признакам показал, что во всех группах наибольшей асимметрией отличаются продольные диаметры костей верхних конечностей. Левосторонняя асимметрия в группах тоболо-иртышских татар в основном характерна для признаков костей нижних конечностей как у мужчин, так и у женщин. Закономерности в половом распределении коэффициентов асимметрии в группах тоболо-иртышских татар выявлены не были. Для наглядности изменчивости коэффициентов асимметрии для мужских и женских групп тоболо-иртышских татар были построены комбинационные полигоны, форма которых показала, что наиболее схожи между собой мужчины тобольских и коурдакско-саргатских татар, а аялынские и тюменские татары заметно отличаются как от этих групп, так и между собой. Формы комбинационных полигонов женских серий тоболо-иртышских татар не обнаруживают видимого сходства между собой. Таким образом, выявленные различия в асимметрии скелетной системы этно-территориальных групп тоболо-иртышских татар, возможно, связаны с хозяйственным укладом жизни татар, который, ввиду различной территории расселения тех или иных этно-территориальных групп, заметно отличался. The article presents the results of studying the limb bone bilateral asymmetry in four groups of the Tobol-Irtysh Tatars: Ayalyn, Tobolsk, Tyumen and Kourdak-Sargat Tatars. The asymmetry coefficients were calculated for the male and female samples of each group (using the R – L formula). The Ayalyn Tatars resulted to have the most symmetric skeletal system, while the Kourdak-Sargat Tatars – the least symmetrical one. The analysis of the asymmetry coefficients of individual bones revealed that the humerus is the most asymmetric bone in both sexes among all the studied groups. The lengths of the upper limb bones resulted to be the most asymmetrical measurement in all groups. Left-sided asymmetry was mainly seen in the lower limb bones among the Tobol-Irtysh Tatars. No sex differences in the asymmetry coefficients were revealed. Combination polygons were produced to illustrate the variability of the asymmetry coefficients for the male and female samples. Male samples of the Tobolsk and Kourdak-Sargat Tatars were found to be most similar to each other, and the Ayalyn and Tyumen Tatars are noticeably different both from these groups and from each other. The combination polygons of the female samples of the Tobol-Irtysh Tatars do not reveal any visible similarity between them. Thus, the revealed differences in the asymmetry of the skeletal system of the Tobol-Irtysh Tatars ethno-territorial groups are possibly associated with different economy systems of the groups.

Risk factors associated with transport gap bending deformity after bone transport in the treatment of lower extremity bone defects caused by infection

Background: The objective of this study was to observe the efficacy of bone transport using Orthofix external fixator in the treatment of lower limb bone defects caused by infection, and analyze the mechanism and risk factors of transport gap bending deformity (TGBD).Methods: From January 2008 to December 2019, 326 cases of infected bone defects of the lower extremities were treated by bone transport in our medical institution. The location and other relevant information of TGBD were collected, summarized, and analyzed. The Association for the Study and Application of the Method of Ilizarov (ASAMI) standard was applied to assess the bone and functional outcomes. Results: A total of 326 patients have reconstructed the bone defects in the lower extremities successfully, with a mean size of 6.2 centimeters (3.4 - 9.1 cm). TGBD was observed in 42 patients (12.8%) after removing the external fixator, including 32 tibias and 10 femurs, after a mean follow-up of 28.6 months (22 – 47 months). Age>45years, BMI>25kg/m2, defect of the tibia, diabetes, osteoporosis, glucocorticoid intake, duration of bone infection>24months, EFT>9months, EFI>1.8months/cm were associated significantly with a higher incidence of TGBD in the binary logistic regression analysis. The independent risk factors associated with TGBD included age>45 years, BMI>25 kg/m2, defect of tibia, diabetes, osteoporosis. Conclusions: The bone transport using the Orthofix external fixator is a safe and practical method in the treatment of lower limb bone defects caused by infection. The incidence of TGBD was 12.8%, and the top five risk factors included defect of tibia, BMI>25kg/m2, duration of bone infection>24 months, age>45years, and diabetes. Age>45years, BMI>25kg/m2, defect of tibia, osteoporosis, diabetes were the independent risk factors. The higher incidence of TGBD may be associated with more risk factors.

New light shed on the early evolution of limb-bone growth plate and bone marrow

The production of blood cells (haematopoiesis) occurs in the limb bones of most tetrapods but is absent in the fin bones of ray-finned fish. When did long bones start producing blood cells? Recent hypotheses suggested that haematopoiesis migrated into long bones prior to the water-to-land transition and protected newly-produced blood cells from harsher environmental conditions. However, little fossil evidence to support these hypotheses has been provided so far. Observations of the humeral microarchitecture of stem-tetrapods, batrachians, and amniotes were performed using classical sectioning and three-dimensional synchrotron virtual histology. They show that Permian tetrapods seem to be among the first to exhibit a centralised marrow organisation, which allows haematopoiesis as in extant amniotes. Not only does our study demonstrate that long-bone haematopoiesis was probably not an exaptation to the water-to-land transition but it sheds light on the early evolution of limb-bone development and the sequence of bone-marrow functional acquisitions.