Ultrashort pulse lasers have significant advantages over conventional continuous wave and long pulse lasers for the texturing of metallic surfaces, especially for nanoscale surface structure patterning. Furthermore, ultrafast laser beam polarization allows for the precise control of the spatial alignment of nanotextures imprinted on titanium-based implant surfaces. In this article, we report the biological effect of beam polarization on human mesenchymal stem cell differentiation. We created, on polished titanium-6aluminum-4vanadium (Ti-6Al-4V) plates, a laser-induced periodic surface structure (LIPSS) using linear or azimuthal polarization of infrared beams to generate linear or radial LIPSS, respectively. The main difference between the two surfaces was the microstructural anisotropy of the linear LIPSS and the isotropy of the radial LIPSS. At 7 d post seeding, cells on the radial LIPSS surface showed the highest extracellular fibronectin production. At 14 days, qRT-PCR showed on the same surface an increase in osteogenesis-related genes, such as alkaline phosphatase and osterix. At 21 d, mineralization clusters indicative of final osteoinduction were more abundant on the radial LIPSS. Taken together, we identified that creating more isotropic than linear surfaces enhances cell differentiation, resulting in an improved osseointegration. Thus, the fine tuning of ultrashort pulse lasers may be a promising new route for the functionalization of medical implants.

Osteopontin (OPN) and Bone Sialoprotein (BSP) are co-expressed in bone and display overlapping and complementary physiological properties. Both genes show a rapid expression response to mechanical stimulation. We used mice with single and double deletions (DKO) of BSP and OPN to assess the specificity of their roles in skeletal adaptation to loading. Two-month-old Wild-Type (WT), BSP knockout (BSP^−/−), OPN^−/− and DKO male mice were submitted to two mechanical stimulation regimen (n = 10 mice/group) respectively impacting trabecular bone (Hypergravity, HG) and cortical bone (Whole Body Vibration, WBV). HG increased trabecular bone volume (BV/TV) in WT femur through reduced resorption, and in BSP^−/− mice femur and vertebra through increased bone formation. In contrast, HG increased the turnover of OPN^−/− bone, resulting in reduced femur and vertebra BV/TV. HG did not affect DKO bones. Similarly, WBV increased cortical thickness in BSP^−/− mice and decreased it in OPN^−/−, without affecting structurally WT and DKO bone. Vibrated BSP^−/− mice displayed increased endocortical bone formation with a drop in Sclerostin expression, and reduced periosteal osteoclasts with lower Rankl and Cathepsin K expression. In contrast, vibrated OPN^−/− endocortical bone displayed decreased formation and increased osteoclast coverage. Therefore, under two regimen (HG and WBV) targeting distinct bone compartments, absence of OPN resulted in bone loss while lack of BSP induced bone gain, reflecting divergent structural adaptations. Strikingly, absence of both proteins led to a relative insensitivity to either mechanical challenge. Interplay between OPN and BSP thus appears as a key element of skeletal response to mechanical stimulation.

Background Interstitial lung disease (ILD) is detected until 60% of patients with rheumatoid arthritis (RA), but is clinically significant in around 10% of cases. It is one of the leading causes of disease and death in RA patients. High levels of anti-cyclic citrullinated peptide (CCP) autoantibodies are associated with co-occurrence of pulmonary disease and RA [1]. Moreover, the pulmonary fibrosis marker mucine (MUC-1) was described to be a predictive indicator for ILD [2]. The adjuvant-induced arthritis (AIA) model is commonly used to investigate arthritic diseases due to some pathophysiological similarities to human arthritis [3]. Objectives The first objective of this study was to investigate the pulmonary involvement occurring in the rat AIA model. The second objective was to investigate the presence of potential biomarkers such as CCP and MUC-1. Methods This study was performed from lungs from 64 AIA rats and 6 control rats without arthritis. Lungs were collected to perform histological and immunological analyses. Pulmonary disease was measured with a score based on the percentage of lung damage and the thickness of the alveolar walls (0: absent, 1: mild, 2: moderate, or 3: severe). CCP and MUC-1 immunostaining was also performed. Results A nonspecific interstitial lung disease was detected in the lungs of 80% of AIA rats, whereas only half control rats developed it. A heterogeneous percentage of lung damage was observed, which correlated with the thickness of the alveolar walls but not with arthritis severity. Granulomas were observed in the most affected lung tissues, with a slight fibrosis at their periphery. The number of CCP markings correlated positively with the percentage of lung damage in AIA rats. MUC-1 was found homogeneously in the lung tissue of control and AIA rats, but more prominently in the periphery of granulomas in AIA rats. Conclusion We have described the pulmonary involvement in the AIA rat model, which developed the extra-articular complication similar to RA-ILD. We identified CCP and MUC-1 as potential biomarkers of this pulmonary involvement. Thus, the lung may be a site of initiation of CCP immunity. The AIA model will then allow a better understanding of RA-ILD, which may lead to earlier diagnosis and the potential development of new targeted therapies. References [1]Aubart F, Crestani B, Nicaise-Roland P, Tubach F, Bollet C, Dawidowicz K, et al. High levels of anti-cyclic citrullinated peptide autoantibodies are associated with co-occurrence of pulmonary diseases with rheumatoid arthritis. J Rheumatol 2011;38:979–982. [2]Elhai M, Avouac J, Allanore Y. Circulating lung biomarkers in idiopathic lung fibrosis and interstitial lung diseases associated with connective tissue diseases: Where do we stand? Semin Arthritis Rheum 2020;50:480–491. [3]Courbon G, Cleret D, Linossier M-T, Vico L, Marotte H. Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model: EARLY BONE LOSS AT ARTHRITIS. J Cell Physiol 2017;232:1318–1325. Available at: http://doi.wiley.com/10.1002/jcp.25601. Accessed October 20, 2020. Acknowledgements: NIL. Disclosure of Interests None Declared.