X-linked hypophosphataemia (XLH) is the most common form of inherited rickets that leads to deformities in the lower limbs, poor tooth and skeletal mineralization, and disproportionate short stature in children. In adults, it is often complicated by enthesopathy, an abnormal mineralization of the tendon-bone attachment. Enthesopathy causes pain and stiffness in affected joints, particularly in the knee, hip, and ankle joints. Enthesopathy is reported as one of the most debilitating symptoms in XLH patients. Previous studies showed that entheses from mice with XLH (Hyp) are characterized by enhanced Bone morphogenic protein (BMP) and Indian hedgehog (IHH) signaling. This study aims to investigate the role of GDF5 in the development of enthesopathy in the Hyp mice. The study has two specific aims: (1) to determine if deleting GDF5 in enthesis (scleraxis-expressing (Scx+)) cells affects BMP/IHH signaling in entheses and (2) to determine if deleting GDF5 in Scx+ cells of Hyp mice attenuates XLH enthesopathy. The study hopes to gain a better understanding of role of GDF5 in enthesis maturation and XLH enthesopathy development. This study finds that deleting GDF5 in wild-type mice does not change normal enthesis maturation. However, deleting GDF5 in Hyp mice attenuates enthesopathy as indicated by decreased BMP/IHH signaling in Hyp entheses. / 2026-03-19T00:00:00Z

Les enthésopathies sur le squelette sont considérées comme des "marqueurs d'activité" en anthropologie biologique. L'étude de tels "marqueurs" pour des fossiles européens du Paléolithique supérieur et du Mésolithique offre l'opportunité d'enrichir notre connaissance des comportements et des modes de vie de ces populations et d'en illustrer certains aspects inconnus, notamment la division sexuelle du travail. Les lacunes méthodologiques (absence de référence médicale et de validation) que présente cette approche m'ont conduit à proposer une nouvelle méthode d'étude. Cette méthode, composée de 4 systèmes de cotation, a été testée sur un échantillon de référence (âge au décès, sexe et activité connus). L'analyse a permis de caractériser une relation entre les modifications osseuses et l'activité physique pour l'un des systèmes. Ce dernier a ensuite été appliqué à un ensemble de fossiles européens du Paléolithique supérieur et du Mésolithique (n = 95) dont les caractéristiques biologiques (âge et sexe) ont été réévaluées au moyen de méthodes fiables. Les résultats attestent de l'intérêt de la démarche. D'une part, ils permettent d'avancer l'hypothèse d'une division sexuelle du travail à ces périodes, avec une pratique du lancer dévolue aux hommes. Ils révèlent d'autre part des différences comportementales entre les populations gravettiennes et celles des périodes plus récentes, impliquant notamment une réduction des distances parcourues et une intensification de l'exploitation du milieu à la fin du Paléolithique supérieur et au Mésolithique. / In bioarchaeology, enthesopathies i.e. "musculoskeletal stress markers" are assumed to reflect the activity of the attaching musculature. The study of enthesopathies in European Upper Palaeolithic and Mesolithic human fossils offers the opportunity to improve our knowledge of the behaviours and lifestyles of these populations and to reveal some unknown aspects like sexual division of labour. The methodological gaps in this approach (e.g. absence of medical reference and validation) led me to propose a new method of studying enthesopathies based on current medical data. This method consists of four scoring systems and has been tested on a reference sample of known age at death, sex and activity. The analysis has established a link between osseous modifications and physical activity for one of the systems. The latter has been applied to a sample of Upper Palaeolithic and Mesolithic fossils (n = 95) after a new assessment of their sex and age at death by using reliable methods. The results give evidence of the relevance of this approach. First, they allow to propose the hypothesis of a sexual division of labour during this period, with throwing activities devolved to men. Second, the results reveal behavioural differences between Gravettian populations and more recent ones, implying a reduction in mobility and an intensification of subsistence activities at the end of the Upper Palaeolithic and during the Mesolithic.