Reconstructing Denisovan Anatomy Using DNA Methylation Maps.

Denisovans are an extinct group of humans whose morphology remains unknown. Here, we present a method for reconstructing skeletal morphology using DNA methylation patterns. Our method is based on linking unidirectional methylation changes to loss-of-function phenotypes. We tested performance by reconstructing Neanderthal and chimpanzee skeletal morphologies and obtained >85% precision in identifying divergent traits. We then applied this method to the Denisovan and offer a putative morphological profile. We suggest that Denisovans likely shared with Neanderthals traits such as an elongated face and a wide pelvis. We also identify Denisovan-derived changes, such as an increased dental arch and lateral cranial expansion. Our predictions match the only morphologically informative Denisovan bone to date, as well as the Xuchang skull, which was suggested by some to be a Denisovan. We conclude that DNA methylation can be used to reconstruct anatomical features, including some that do not survive in the fossil record.

Standing Up for Sticklebacks.

The morphology of the vertebrate skeleton exhibits tremendous plasticity in evolution, allowing adaptation to a wide variety of ecological niches and lifestyles. Indjeian et al. now uncover how the cis regulation of a gene controls skeletal variation in fish and might have contributed to the evolution of bipedalism in humans.

Evolving New Skeletal Traits by cis-Regulatory Changes in Bone Morphogenetic Proteins.

Changes in bone size and shape are defining features of many vertebrates. Here we use genetic crosses and comparative genomics to identify specific regulatory DNA alterations controlling skeletal evolution. Armor bone-size differences in sticklebacks map to a major effect locus overlapping BMP family member GDF6. Freshwater fish express more GDF6 due in part to a transposon insertion, and transgenic overexpression of GDF6 phenocopies evolutionary changes in armor-plate size. The human GDF6 locus also has undergone distinctive regulatory evolution, including complete loss of an enhancer that is otherwise highly conserved between chimps and other mammals. Functional tests show that the ancestral enhancer drives expression in hindlimbs but not forelimbs, in locations that have been specifically modified during the human transition to bipedalism. Both gain and loss of regulatory elements can localize BMP changes to specific anatomical locations, providing a flexible regulatory basis for evolving species-specific changes in skeletal form.

New reptile shows dinosaurs and pterosaurs evolved among diverse precursors.

Dinosaurs and pterosaurs have remarkable diversity and disparity through most of the Mesozoic Era1-3. Soon after their origins, these reptiles diversified into a number of long-lived lineages, evolved unprecedented ecologies (for example, flying, large herbivorous forms) and spread across Pangaea4,5. Recent discoveries of dinosaur and pterosaur precursors6-10 demonstrated that these animals were also speciose and widespread, but those precursors have few if any well-preserved skulls, hands and associated skeletons11,12. Here we present a well-preserved partial skeleton (Upper Triassic, Brazil) of the new lagerpetid Venetoraptor gassenae gen. et sp. nov. that offers a more comprehensive look into the skull and ecology of one of these precursors. Its skull has a sharp, raptorial-like beak, preceding that of dinosaurs by around 80 million years, and a large hand with long, trenchant claws that firmly establishes the loss of obligatory quadrupedalism in these precursor lineages. Combining anatomical information of the new species with other dinosaur and pterosaur precursors shows that morphological disparity of precursors resembles that of Triassic pterosaurs and exceeds that of Triassic dinosaurs. Thus, the 'success' of pterosaurs and dinosaurs was a result of differential survival among a broader pool of ecomorphological variation. Our results show that the morphological diversity of ornithodirans started to flourish among early-diverging lineages and not only after the origins of dinosaurs and pterosaurs.

A heavyweight early whale pushes the boundaries of vertebrate morphology.

The fossil record of cetaceans documents how terrestrial animals acquired extreme adaptations and transitioned to a fully aquatic lifestyle1,2. In whales, this is associated with a substantial increase in maximum body size. Although an elongate body was acquired early in cetacean evolution3, the maximum body mass of baleen whales reflects a recent diversification that culminated in the blue whale4. More generally, hitherto known gigantism among aquatic tetrapods evolved within pelagic, active swimmers. Here we describe Perucetus colossus-a basilosaurid whale from the middle Eocene epoch of Peru. It displays, to our knowledge, the highest degree of bone mass increase known to date, an adaptation associated with shallow diving5. The estimated skeletal mass of P. colossus exceeds that of any known mammal or aquatic vertebrate. We show that the bone structure specializations of aquatic mammals are reflected in the scaling of skeletal fraction (skeletal mass versus whole-body mass) across the entire disparity of amniotes. We use the skeletal fraction to estimate the body mass of P. colossus, which proves to be a contender for the title of heaviest animal on record. Cetacean peak body mass had already been reached around 30 million years before previously assumed, in a coastal context in which primary productivity was particularly high.

Environmental signal in the evolutionary diversification of bird skeletons.

Characterizing how variation in the tempo and mode of evolution has structured the phenotypic diversity of extant species is a central goal of macroevolution1-3. However, studies are typically limited to a handful of traits4-6, providing incomplete information. We analyse morphological diversification in living birds, an ecologically diverse group7, documenting structural scales from 'pan-skeletal' proportions down to the localized three-dimensional shape changes of individual bones. We find substantial variation in evolutionary modes among avian subgroups and among skeletal parts, indicating widespread mosaicism and possible differences in the structure of the macroevolutionary landscape across Earth's main environments. Water-linked groups, especially Aequorlitornithes (waterbirds), have repeatedly explored a large portion of their total morphospace, emphasizing variation in body proportions and in the shape of bones close to the body core, which are functionally related to the mechanics of locomotion8. By contrast, landbirds (Inopinaves) evolved distinct, group-specific body forms early in the aftermath of the K-Pg and subsequently emphasized local shape variation, especially in the head and distal limb bones, which interact more directly with the environment. Passerines, which comprise more than half of all bird species, show a conservative evolutionary dynamic that resulted in low disparity across all skeletal parts. Evidence for early establishment of the morphospace of living birds is clear for some skeletal parts, including beaks and the combined skeletal morphology. However, we find little evidence for early partitioning of that morphospace, contrary to more specific predictions of 'niche-filling' models1,9. Nevertheless, early divergence among broad environmental types may have caused an early divergence of evolutionary modes, suggesting an important role for environmental divergence in structuring the radiation of crown-group birds.

Africa's oldest dinosaurs reveal early suppression of dinosaur distribution.

The vertebrate lineages that would shape Mesozoic and Cenozoic terrestrial ecosystems originated across Triassic Pangaea1-11. By the Late Triassic (Carnian stage, ~235 million years ago), cosmopolitan 'disaster faunas' (refs. 12-14) had given way to highly endemic assemblages12,13 on the supercontinent. Testing the tempo and mode of the establishment of this endemism is challenging-there were few geographic barriers to dispersal across Pangaea during the Late Triassic. Instead, palaeolatitudinal climate belts, and not continental boundaries, are proposed to have controlled distribution15-18. During this time of high endemism, dinosaurs began to disperse and thus offer an opportunity to test the timing and drivers of this biogeographic pattern. Increased sampling can test this prediction: if dinosaurs initially dispersed under palaeolatitudinal-driven endemism, then an assemblage similar to those of South America4,19-21 and India19,22-including the earliest dinosaurs-should be present in Carnian deposits in south-central Africa. Here we report a new Carnian assemblage from Zimbabwe that includes Africa's oldest definitive dinosaurs, including a nearly complete skeleton of the sauropodomorph Mbiresaurus raathi gen. et sp. nov. This assemblage resembles other dinosaur-bearing Carnian assemblages, suggesting that a similar vertebrate fauna ranged high-latitude austral Pangaea. The distribution of the first dinosaurs is correlated with palaeolatitude-linked climatic barriers, and dinosaurian dispersal to the rest of the supercontinent was delayed until these barriers relaxed, suggesting that climatic controls influenced the initial composition of the terrestrial faunas that persist to this day.

Bizarre tail weaponry in a transitional ankylosaur from subantarctic Chile.

Armoured dinosaurs are well known for their evolution of specialized tail weapons-paired tail spikes in stegosaurs and heavy tail clubs in advanced ankylosaurs1. Armoured dinosaurs from southern Gondwana are rare and enigmatic, but probably include the earliest branches of Ankylosauria2-4. Here we describe a mostly complete, semi-articulated skeleton of a small (approximately 2 m) armoured dinosaur from the late Cretaceous period of Magallanes in southernmost Chile, a region that is biogeographically related to West Antarctica5. Stegouros elengassen gen. et sp. nov. evolved a large tail weapon unlike any dinosaur: a flat, frond-like structure formed by seven pairs of laterally projecting osteoderms encasing the distal half of the tail. Stegouros shows ankylosaurian cranial characters, but a largely ancestral postcranial skeleton, with some stegosaur-like characters. Phylogenetic analyses placed Stegouros in Ankylosauria; specifically, it is related to Kunbarrasaurus from Australia6 and Antarctopelta from Antarctica7, forming a clade of Gondwanan ankylosaurs that split earliest from all other ankylosaurs. The large osteoderms and specialized tail vertebrae in Antarctopelta suggest that it had a tail weapon similar to Stegouros. We propose a new clade, the Parankylosauria, to include the first ancestor of Stegouros-but not Ankylosaurus-and all descendants of that ancestor.

Fossoriality and evolutionary development in two Cretaceous mammaliamorphs.

Mammaliamorpha comprises the last common ancestor of Tritylodontidae and Mammalia plus all its descendants1. Tritylodontids are nonmammaliaform herbivorous cynodonts that originated in the Late Triassic epoch, diversified in the Jurassic period2-5 and survived into the Early Cretaceous epoch6,7. Eutriconodontans have generally been considered to be an extinct mammalian group, although different views exist8. Here we report a newly discovered tritylodontid and eutriconodontan from the Early Cretaceous Jehol Biota of China. Eutriconodontans are common in this biota9, but it was not previously known to contain tritylodontids. The two distantly related species show convergent features that are adapted for fossorial life, and are the first 'scratch-diggers' known from this biota. Both species also show an increased number of presacral vertebrae, relative to the ancestral state in synapsids or mammals10,11, that display meristic and homeotic changes. These fossils shed light on the evolutionary development of the axial skeleton in mammaliamorphs, which has been the focus of numerous studies in vertebrate evolution12-17 and developmental biology18-28. The phenotypes recorded by these fossils indicate that developmental plasticity in somitogenesis and HOX gene expression in the axial skeleton-similar to that observed in extant mammals-was already in place in stem mammaliamorphs. The interaction of these developmental mechanisms with natural selection may have underpinned the diverse phenotypes of body plan that evolved independently in various clades of mammaliamorph.

Earliest known human burial in Africa.

The origin and evolution of hominin mortuary practices are topics of intense interest and debate1-3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1-6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS), a cave site in the tropical upland coast of Kenya7,8. Recent excavations have revealed a pit feature containing a child in a flexed position. Geochemical, granulometric and micromorphological analyses of the burial pit content and encasing archaeological layers indicate that the pit was deliberately excavated. Taphonomical evidence, such as the strict articulation or good anatomical association of the skeletal elements and histological evidence of putrefaction, support the in-place decomposition of the fresh body. The presence of little or no displacement of the unstable joints during decomposition points to an interment in a filled space (grave earth), making the PYS finding the oldest known human burial in Africa. The morphological assessment of the partial skeleton is consistent with its assignment to Homo sapiens, although the preservation of some primitive features in the dentition supports increasing evidence for non-gradual assembly of modern traits during the emergence of our species. The PYS burial sheds light on how MSA populations interacted with the dead.

Thrombospondins modulate cell function and tissue structure in the skeleton.

Thrombospondins (TSPs) belong to a functional class of ECM proteins called matricellular proteins that are not primarily structural, but instead influence cellular interactions within the local extracellular environment. The 3D arrangement of TSPs allow interactions with other ECM proteins, sequestered growth factors, and cell surface receptors. They are expressed in mesenchymal condensations and limb buds during skeletal development, but they are not required for patterning. Instead, when absent, there are alterations in musculoskeletal connective tissue ECM structure, organization, and function, as well as altered skeletal cell phenotypes. Both functional redundancies and unique contributions to musculoskeletal tissue structure and physiology are revealed in mouse models with compound TSP deletions. Crucial roles of individual TSPs are revealed during musculoskeletal injury and regeneration. The interaction of TSPs with mesenchymal stem cells (MSC), and their influence on cell fate, function, and ultimately, musculoskeletal phenotype, suggest that TSPs play integral, but as yet poorly understood roles in musculoskeletal health. Here, unique and overlapping contributions of trimeric TSP1/2 and pentameric TSP3/4/5 to musculoskeletal cell and matrix physiology are reviewed. Opportunities for new research are also noted.

Skeleton of a Cretaceous mammal from Madagascar reflects long-term insularity.

The fossil record of mammaliaforms (mammals and their closest relatives) of the Mesozoic era from the southern supercontinent Gondwana is far less extensive than that from its northern counterpart, Laurasia1,2. Among Mesozoic mammaliaforms, Gondwanatheria is one of the most poorly known clades, previously represented by only a single cranium and isolated jaws and teeth1-5. As a result, the anatomy, palaeobiology and phylogenetic relationships of gondwanatherians remain unclear. Here we report the discovery of an articulated and very well-preserved skeleton of a gondwanatherian of the latest age (72.1-66 million years ago) of the Cretaceous period from Madagascar that we assign to a new genus and species, Adalatherium hui. To our knowledge, the specimen is the most complete skeleton of a Gondwanan Mesozoic mammaliaform that has been found, and includes the only postcranial material and ascending ramus of the dentary known for any gondwanatherian. A phylogenetic analysis including the new taxon recovers Gondwanatheria as the sister group to Multituberculata. The skeleton, which represents one of the largest of the Gondwanan Mesozoic mammaliaforms, is particularly notable for exhibiting many unique features in combination with features that are convergent on those of therian mammals. This uniqueness is consistent with a lineage history for A. hui of isolation on Madagascar for more than 20 million years.

Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton.

Insulin-like growth factor I (IGF-1) is a key regulator of tissue growth and development in response to growth hormone stimulation. In the skeletal system, IGF-1 derived from osteoblasts and chondrocytes are essential for normal bone development; however, whether bone marrow (BM)-resident cells provide distinct sources of IGF-1 in the adult skeleton remains elusive. Here, we show that BM stromal cells (BMSCs) and megakaryocytes/platelets (MKs/PLTs) express the highest levels of IGF-1 in adult long bones. Deletion of Igf1 from BMSCs by Lepr-Cre leads to decreased bone formation, impaired bone regeneration, and increased BM adipogenesis. Importantly, reduction of BMSC-derived IGF-1 contributes to fasting-induced marrow fat accumulation. In contrast, deletion of Igf1 from MKs/PLTs by Pf4-Cre leads to reduced bone formation and regeneration without affecting BM adipogenesis. To our surprise, MKs/PLTs are also an important source of systemic IGF-1. Platelet-rich plasma (PRP) from Pf4-Cre; Igf1f/fmice showed compromised osteogenic potential both in vivo and in vitro, suggesting that MK/PLT-derived IGF-1 underlies the therapeutic effects of PRP. Taken together, this study identifies BMSCs and MKs/PLTs as two important sources of IGF-1 that coordinate to maintain and regenerate the adult skeleton, highlighting reciprocal regulation between the hematopoietic and skeletal systems.

The BMP Pathway and Its Inhibitors in the Skeleton.

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor-ß family of ligands. BMPs exhibit widespread utility and pleiotropic, context-dependent effects, and the strength and duration of BMP pathway signaling is tightly regulated at numerous levels via mechanisms operating both inside and outside the cell. Defects in the BMP pathway or its regulation underlie multiple human diseases of different organ systems. Yet much remains to be discovered about the BMP pathway in its original context, i.e., the skeleton. In this review, we provide a comprehensive overview of the intricacies of the BMP pathway and its inhibitors in bone development, homeostasis, and disease. We frame the content of the review around major unanswered questions for which incomplete evidence is available. First, we consider the gene regulatory network downstream of BMP signaling in osteoblastogenesis. Next, we examine why some BMP ligands are more osteogenic than others and what factors limit BMP signaling during osteoblastogenesis. Then we consider whether specific BMP pathway components are required for normal skeletal development, and if the pathway exerts endogenous effects in the aging skeleton. Finally, we propose two major areas of need of future study by the field: greater resolution of the gene regulatory network downstream of BMP signaling in the skeleton, and an expanded repertoire of reagents to reliably and specifically inhibit individual BMP pathway components.

Cosmogenic nuclide dating of Australopithecus at Sterkfontein, South Africa.

Sterkfontein is the most prolific single source of Australopithecus fossils, the vast majority of which were recovered from Member 4, a cave breccia now exposed by erosion and weathering at the landscape surface. A few other Australopithecus fossils, including the StW 573 skeleton, come from subterranean deposits [T. C. Partridge et al., Science 300, 607-612 (2003); R. J. Clarke, K. Kuman, J. Hum. Evol. 134, 102634 (2019)]. Here, we report a cosmogenic nuclide isochron burial date of 3.41 ± 0.11 million years (My) within the lower middle part of Member 4, and simple burial dates of 3.49 ± 0.19 My in the upper middle part of Member 4 and 3.61 ± 0.09 My in Jacovec Cavern. Together with a previously published isochron burial date of 3.67 ± 0.16 My for StW 573 [D. E. Granger et al., Nature 522, 85-88 (2015)], these results place nearly the entire Australopithecus assemblage at Sterkfontein in the mid-Pliocene, contemporaneous with Australopithecus afarensis in East Africa. Our ages for the fossil-bearing breccia in Member 4 are considerably older than the previous ages of ca. 2.1 to 2.6 My interpreted from flowstones associated with the same deposit. We show that these previously dated flowstones are stratigraphically intrusive within Member 4 and that they therefore underestimate the true age of the fossils.

High-Mg calcite nanoparticles within a low-Mg calcite matrix: A widespread phenomenon in biomineralization.

During the process of biomineralization, organisms utilize various biostrategies to enhance the mechanical durability of their skeletons. In this work, we establish that the presence of high-Mg nanoparticles embedded within lower-Mg calcite matrices is a widespread strategy utilized by various organisms from different kingdoms and phyla to improve the mechanical properties of their high-Mg calcite skeletons. We show that such phase separation and the formation of high-Mg nanoparticles are most probably achieved through spinodal decomposition of an amorphous Mg-calcite precursor. Such decomposition is independent of the biological characteristics of the studied organisms belonging to different phyla and even kingdoms but rather, originates from their similar chemical composition and a specific Mg content within their skeletons, which generally ranges from 14 to 48 mol % of Mg. We show evidence of high-Mg calcite nanoparticles in the cases of six biologically different organisms all demonstrating more than 14 mol % Mg-calcite and consider it likely that this phenomenon is immeasurably more prevalent in nature. We also establish the absence of these high-Mg nanoparticles in organisms whose Mg content is lower than 14 mol %, providing further evidence that whether or not spinodal decomposition of an amorphous Mg-calcite precursor takes place is determined by the amount of Mg it contains. The valuable knowledge gained from this biostrategy significantly impacts the understanding of how biominerals, although composed of intrinsically brittle materials, can effectively resist fracture. Moreover, our theoretical calculations clearly suggest that formation of Mg-rich nanoprecipitates greatly enhances the hardness of the biomineralized tissue as well.

An integrative skeletal and paleogenomic analysis of stature variation suggests relatively reduced health for early European farmers.

Human culture, biology, and health were shaped dramatically by the onset of agriculture ∼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared "predicted" genetic contributions to height from paleogenomic data and "achieved" adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (∼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

Development of the vertebra and fin skeleton in the lamprey and its implications for the homology of vertebrate vertebrae.

BACKGROUND: Although vertebrae are the defining character of vertebrates, they are found only in rudimentary form in extant agnathans. In addition, the vertebrae of agnathans possess several unique features, such as elastin-like molecules as the main matrix component and late (post-metamorphosis) differentiation of lamprey vertebrae. In this study, by tracing the developmental process of vertebrae in lamprey, we examined the homology of vertebrae between lampreys and gnathostomes. RESULTS: We found that the lamprey somite is first subdivided mediolaterally, with myotome cells differentiating medially and non-myotome cells emerging laterally. Subsequently, collagen-positive non-myotome cells surround the myotome. This pattern of somitogenesis is rather similar to that in amphioxi and sheds doubt on the presence of a sclerotome, in terms of mesenchyme cells induced by a signal from the notochord, in lamprey. Further tracing of non-myotome cell development revealed that fin cartilage develops in ammocoete larvae approximately 35 mm in body length. The development of the fin cartilage occurs much earlier than that of the vertebra whose development proceeds during metamorphosis. CONCLUSION: We propose that the homology of vertebrae between agnathans and gnathostomes should be discussed carefully, because the developmental process of the lamprey vertebra is different from that of gnathostomes.

Diverse triterpene skeletons are derived from the expansion and divergent evolution of 2,3-oxidosqualene cyclases in plants.

Triterpenoids are one of the largest groups of secondary metabolites and exhibit diverse structures, which are derived from C30 skeletons that are biosynthesized via the isoprenoid pathway by cyclization of 2,3-oxidosqualene. Triterpenoids have a wide range of biological activities, and are used in functional foods, drugs, and as industrial materials. Due to the low content levels in their native plants and limited feasibility and efficiency of chemical synthesis, heterologous biosynthesis of triterpenoids is the most promising strategy. Herein, we classified 121 triterpene alcohols/ketones according to their conformation and ring numbers, among which 51 skeletons have been experimentally characterized as the products of oxidosqualene cyclases (OSCs). Interestingly, 24 skeletons that have not been reported from nature source were generated by OSCs in heterologous expression. Comprehensive evolutionary analysis of the identified 152 OSCs from 75 species in 25 plant orders show that several pentacyclic triterpene synthases repeatedly originated in multiple plant lineages. Comparative analysis of OSC catalytic reaction revealed that stabilization of intermediate cations, steric hindrance, and conformation of active center amino acid residues are primary factors affecting triterpene formation. Optimization of OSC could be achieved by changing of side-chain orientations of key residues. Recently, methods, such as rationally design of pathways, regulation of metabolic flow, compartmentalization engineering, etc., were introduced in improving chassis for the biosynthesis of triterpenoids. We expect that extensive study of natural variation of large number of OSCs and catalytical mechanism will provide basis for production of high level of triterpenoids by application of synthetic biology strategies.

Tension regulates the cartilage phenotypic expression of endplate chondrocytes through the α-catenin/actin skeleton/Hippo pathway.

The study aimed to investigate the regulatory mechanism of intracellular tension signaling in endplate chondrocytes and its impact on extracellular matrix synthesis. Human endplate chondrocytes were subjected to tension load using Flexcell FX-5000™, and changes in phenotype, morphology, and the expression of Hippo signaling pathway and α-Catenin were assessed through various techniques. Through the overexpression of YAP and inhibition of α-Catenin, the study clarified the intracellular tension signaling pathway and its regulation of extracellular matrix synthesis in endplate cartilage. In vitro-cultured human endplate chondrocytes significantly suppressed phenotype-related genes and proteins, accompanied by distinct changes in cytoskeleton morphology. Tension activation resulted in the substantial activation of the Hippo pathway, increased phosphorylation of YAP, and reduced nuclear translocation of YAP. YAP overexpression alleviated the inhibitory effect of tension on extracellular matrix synthesis in endplate chondrocytes. Tension also upregulated the expression of α-Catenin in endplate chondrocytes, which was attenuated by inhibiting α-Catenin expression, thereby reducing the impact of tension on cytoskeletal morphology and YAP nuclear translocation. Taken together, the α-Catenin/actin skeleton/Hippo-coupled network is a crucial signaling pathway for tension signaling in endplate chondrocytes, providing potential therapeutic targets for the treatment of endplate cartilage degeneration.