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1. Mechanosensitive Control of Articular Cartilage and Subchondral Bone Homeostasis in Mice Requires Osteocytic Transforming Growth Factor β Signaling

   https://doi.org/10.1002/art.41548  

   Bailey, Karsyn N. ; Nguyen, Jeffrey ; Yee, Cristal S. ; Dole, Neha S. ; Dang, Alexis ; Alliston, Tamara ( February 2021 , Arthritis & Rheumatology)

   Transforming growth factor β (TGFβ) signaling plays a complex tissue‐specific and nonlinear role in osteoarthritis (OA). This study was conducted to determine the osteocytic contributions of TGFβ signaling to OA.

   To identify the role of osteocytic TGFβ signaling in joint homeostasis, we used 16‐week‐old male mice (n = 9–11 per group) and female mice (n = 7–11 per group) with an osteocyte‐intrinsic ablation of TGFβ receptor type II (TβRII^ocy−/−mice) and assessed defects in cartilage degeneration, subchondral bone plate (SBP) thickness, and SBP sclerostin expression. To further investigate these mechanisms in 16‐week‐old male mice, we perturbed joint homeostasis by subjecting 8‐week‐old mice to medial meniscal/ligamentous injury (MLI), which preferentially disrupts the mechanical environment of the medial joint to induce OA.

   In all contexts, independent of sex, genotype, or medial or lateral joint compartment, increased SBP thickness and SBP sclerostin expression were spatially associated with cartilage degeneration. Male TβRII^ocy−/−mice, but not female TβRII^ocy−/−mice, had increased cartilage degeneration, increased SBP thickness, and higher levels of SBP sclerostin compared with control mice (allP< 0.05), demonstrating that the role of osteocytic TGFβ signaling on joint homeostasis is sexually dimorphic. With changes in joint mechanics following injury, control mice had increased SBP thickness, subchondral bone volume, and SBP sclerostin expression (allP< 0.05). TβRII^ocy−/−mice, however, were insensitive to subchondral bone changes with injury, suggesting that mechanosensation at the SBP requires osteocytic TGFβ signaling.

   Our results provide new evidence that osteocytic TGFβ signaling is required for a mechanosensitive response to injury, and that osteocytes control SBP homeostasis to maintain cartilage health, identifying osteocytic TGFβ signaling as a novel therapeutic target for OA.

    

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2. A life-history perspective on sexual selection in a polygamous species

   https://doi.org/10.1186/s12862-020-01618-3  

   Gao, Ke ; van Wijk, Michiel ; Clement, Zoe ; Egas, Martijn ; Groot, Astrid T. ( May 2020 , BMC Evolutionary Biology)

   Ever since Darwin, evolutionary biologists have studied sexual selection driving differences in appearance and behaviour between males and females. An unchallenged paradigm in such studies is that one sex (usually the male) signals its quality as a mate to the other sex (usually the female), who is choosy in accepting a partner. Here, we hypothesize that in polygamous species these roles change dynamically with the mating status of males and females, depending on direct reproductive costs and benefits of multiple matings, and on sperm competition. We test this hypothesis by assessing fitness costs and benefits of multiple matings in both males and females in a polygamous moth species, as in moths not males but females are the signalers and males are the responders.

   We found that multiple matings confer fitness costs and benefits for both sexes. Specifically, the number of matings did not affect the longevity of males or females, but only 67% of the males and 14% of the females mated successfully in all five nights. In addition, the female’s reproductive output increased with multiple matings, although when paired with a new virgin male every night, more than 3 matings decreased her reproductive output, so that the Bateman gradient for females fit a quadratic model better than a linear model. The male’s reproductive success was positively affected by the number of matings and a linear regression line best fit the data. Simulations of the effect of sperm competition showed that increasing last-male paternity increases the steepness of the male Bateman gradient and thus the male’s relative fitness gain from additional mating. Irrespective of last-male paternity value, the female Bateman gradient is steeper than the male one for up to three matings.

   Our results suggest that choosiness in moths may well change throughout the mating season, with males being more choosy early in the season and females being more choosy after having mated at least three times. This life-history perspective on the costs and benefits of multiple matings for both sexes sheds new light on sexual selection forces acting on sexual signals and responses.

    

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3. Female‐directed aggression by adolescent male chimpanzees primarily constitutes dominance striving, not sexual coercion

   https://doi.org/10.1002/ajpa.24296  

   Enigk, Drew K. ; Emery Thompson, Melissa ; Machanda, Zarin P. ; Wrangham, Richard W. ; Muller, Martin N. ( May 2021 , American Journal of Physical Anthropology)

   Chimpanzees (Pan troglodytes) are notable for exhibiting high levels of male‐to‐female aggression. Much of this aggression from adult males serves sexually coercive functions. Despite being smaller and lower‐ranking than adult males, adolescent males also engage in regular aggression against adult females. Here, we test whether the primary function of this aggression is sexual coercion, as in adult males, or, alternatively, whether adolescent males use aggression to establish social dominance over females.

   We analyzed 1771 copulations and 1812 instances of male‐initiated aggression between adolescent males (aged nine through 14 years) and adult females across 21 years of observation of the Kanyawara chimpanzee community in Kibale National Park, Uganda.

   Our test of the sexual coercion hypothesis revealed that adolescent males did not selectively target cycling females for aggression, nor did aggression against cycling females predict rates of copulation with those females. Our test of the social dominance hypothesis showed that males succeeded in dominating all adult females before, or soon after, dominating their first adult male. Additionally, we found that adolescent males dominated females approximately in the order of the females' own ranks, from the bottom to the top of the female hierarchy.

   Our data illustrate that the establishment of social dominance was more important than sexual coercion in explaining patterns of adolescent male aggression toward females. In comparison, evidence for sexual coercion was clear and compelling in adult males. These findings highlight that the primary function of male‐to‐female aggression differs between adolescent and adult males.

    

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4. Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture

   https://doi.org/10.1038/s41598-020-73270-2  

   Wang, Yuyan ; Gludish, David W. ; Hayashi, Kei ; Todhunter, Rory J. ; Krotscheck, Ursula ; Johnson, Philippa J. ; Cummings, Bethany P. ; Su, Jin ; Reesink, Heidi L. ( October 2020 , Scientific Reports)

   Lubricin is an important boundary lubricant and chondroprotective glycoprotein in synovial fluid. Both increased and decreased synovial fluid lubricin concentrations have been reported in experimental post-traumatic osteoarthritis (PTOA) animal models and in naturally occurring joint injuries in humans and animals, with no consensus about how lubricin is altered in different species or injury types. Increased synovial fluid lubricin has been observed following intra-articular fracture in humans and horses and in human late-stage osteoarthritis; however, it is unknown how synovial lubricin is affected by knee-destabilizing injuries in large animals. Spontaneous rupture of cranial cruciate ligament (RCCL), the anterior cruciate ligament equivalent in quadrupeds, is a common injury in dogs often accompanied by OA. Here, clinical records, radiographs, and synovial fluid samples from 30 dogs that sustained RCCL and 9 clinically healthy dogs were analyzed. Synovial fluid lubricin concentrations were nearly 16-fold greater in RCCL joints as compared to control joints, while IL-2, IL-6, IL-8, and TNF-α concentrations did not differ between groups. Synovial fluid lubricin concentrations were correlated with the presence of radiographic OA and were elevated in three animals sustaining RCCL injury prior to the radiographic manifestation of OA, indicating that lubricin may be a potential biomarker for early joint injury.

    

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5. Spatial Gradients of Quantitative MRI as Biomarkers for Early Detection of Osteoarthritis: Data From Human Explants and the Osteoarthritis Initiative

   https://doi.org/10.1002/jmri.28471  

   Wilson, Robert L. ; Emery, Nancy C. ; Pierce, David M. ; Neu, Corey P. ( October 2022 , Journal of Magnetic Resonance Imaging)

   Healthy articular cartilage presents structural gradients defined by distinct zonal patterns through the thickness, which may be disrupted in the pathogenesis of several disorders. Analysis of textural patterns using quantitative MRI data may identify structural gradients of healthy or degenerating tissue that correlate with early osteoarthritis (OA).

   To quantify spatial gradients and patterns in MRI data, and to probe new candidate biomarkers for early severity of OA.

   Retrospective study.

   Fourteen volunteers receiving total knee replacement surgery (eight males/two females/four unknown, average age ± standard deviation: 68.1 ± 9.6 years) and 10 patients from the OA Initiative (OAI) with radiographic OA onset (two males/eight females, average age ± standard deviation: 57.7 ± 9.4 years; initial Kellgren‐Lawrence [KL] grade: 0; final KL grade: 3 over the 10‐year study).

   3.0‐T and 14.1‐T, biomechanics‐based displacement‐encoded imaging, fast spin echo, multi‐slice multi‐echoT2mapping.

   We studied structure and strain in cartilage explants from volunteers receiving total knee replacement, or structure in cartilage of OAI patients with progressive OA. We calculated spatial gradients of quantitative MRI measures (eg, T2) normal to the cartilage surface to enhance zonal variations. We compared gradient values against histologically OA severity, conventional relaxometry, and/or KL grades.

   Multiparametric linear regression for evaluation of the relationship between residuals of the mixed effects models and histologically determined OA severity scoring, with a significance threshold atα = 0.05.

   Gradients of individual relaxometry and biomechanics measures significantly correlated with OA severity, outperforming conventional relaxometry and strain metrics. In human explants, analysis of spatial gradients provided the strongest relationship to OA severity (R² = 0.627). Spatial gradients of T2 from OAI data identified variations in radiographic (KL Grade 2) OA severity in single subjects, while conventional T2 alone did not.

   Spatial gradients of quantitative MRI data may improve the predictive power of noninvasive imaging for early‐stage degeneration.

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