Influence de la localisation anatomique des cartilages sur leur composition et leur réponse biologique au stress inflammatoire

Osteoarthritis of the hand is the second most common location of symptomatic osteoarthritis after the knee. Several studies have suggested that the properties of cartilage depend on its anatomical location. We compared cartilage from proximal interphalangeal (PPI), metacarpophalangeal (MCP) and knee joints from recently deceased human donors. Cell density was inversely correlated with cartilage thickness. The levels of homocitrulline (HCit) and carboxymethyllysine (CML), post-translational modifications of proteins related to ageing, varied according to anatomical location. Non-arthritic cartilages had different baseline secretion profiles depending on their location: PPIs secreted less MMP-3 than PCMs. Under the influence of a pro-inflammatory stimulus (IL-1β), the increase in IL-6 secretion was 6-fold greater in knees than in PPIs, that of MMP-3 greater in PPIs than in PCMs and knees. IL-1β-stimulated OA cartilage showed greater increases in IL-6 and PGE2 secretion at the knees than at the PPIs. Finally, serum HCit and CML levels did not correlate with the severity of radiographic damage in a cohort of patients with hand OA. Overall, there are differences in biochemical composition, and biological functional differences between digital and knee cartilage. The development of new therapeutic approaches must take this variability into account.L'arthrose de la main est la deuxième localisation d'arthrose symptomatique après le genou. Plusieurs études ont suggéré que les propriétés du cartilage dépendaient de sa localisation anatomique. Nous avons comparé des cartilages d’articulations inter-phalangiennes proximales (IPP), métacarpo-phalangiennes (MCP) et de genoux issus de donneurs humains récemment décédés. La densité cellulaire était inversement corrélée à l’épaisseur du cartilage considéré. Les taux d’homocitrulline (HCit) et de carboxymethyllysine (CML), modifications post-traductionnelles des protéines liées au vieillissement, variaient suivant la localisation anatomique. Les cartilages non arthrosiques avaient des profils de sécrétion de base différents selon leur localisation: les IPP sécrétaient moins de MMP-3 que les MCP. Sous l’influence d’un stimulus pro-inflammatoire (IL-1β), l’accroissement de sécrétion de l’IL-6 était 6 fois plus importante aux genoux qu’aux IPP, celui de la MMP-3 plus important aux IPP qu’aux MCP et qu’aux genoux. Les cartilages arthrosiques stimulés par l’IL-1β montraient des accroissements de sécrétion de l’IL-6 et de la PGE2 plus importants aux genoux qu’aux IPP. Enfin, les taux sériques d’HCit et de CML n’étaient pas corrélés à la sévérité de l’atteinte radiolographique dans une cohorte de patients souffrant d’arthrose des mains. Au total, il existe des différences de composition biochimique, et des différences fonctionnelles biologiques entre les cartilages digitaux et de genoux. Le développement de nouvelles approches thérapeutiques doit prendre en compte cette variabilité

Influence de la localisation anatomique des cartilages sur leur composition et leur réponse biologique au stress inflammatoire

Osteoarthritis of the hand is the second most common location of symptomatic osteoarthritis after the knee. Several studies have suggested that the properties of cartilage depend on its anatomical location. We compared cartilage from proximal interphalangeal (PPI), metacarpophalangeal (MCP) and knee joints from recently deceased human donors. Cell density was inversely correlated with cartilage thickness. The levels of homocitrulline (HCit) and carboxymethyllysine (CML), post-translational modifications of proteins related to ageing, varied according to anatomical location. Non-arthritic cartilages had different baseline secretion profiles depending on their location: PPIs secreted less MMP-3 than PCMs. Under the influence of a pro-inflammatory stimulus (IL-1β), the increase in IL-6 secretion was 6-fold greater in knees than in PPIs, that of MMP-3 greater in PPIs than in PCMs and knees. IL-1β-stimulated OA cartilage showed greater increases in IL-6 and PGE2 secretion at the knees than at the PPIs. Finally, serum HCit and CML levels did not correlate with the severity of radiographic damage in a cohort of patients with hand OA. Overall, there are differences in biochemical composition, and biological functional differences between digital and knee cartilage. The development of new therapeutic approaches must take this variability into account.L'arthrose de la main est la deuxième localisation d'arthrose symptomatique après le genou. Plusieurs études ont suggéré que les propriétés du cartilage dépendaient de sa localisation anatomique. Nous avons comparé des cartilages d’articulations inter-phalangiennes proximales (IPP), métacarpo-phalangiennes (MCP) et de genoux issus de donneurs humains récemment décédés. La densité cellulaire était inversement corrélée à l’épaisseur du cartilage considéré. Les taux d’homocitrulline (HCit) et de carboxymethyllysine (CML), modifications post-traductionnelles des protéines liées au vieillissement, variaient suivant la localisation anatomique. Les cartilages non arthrosiques avaient des profils de sécrétion de base différents selon leur localisation: les IPP sécrétaient moins de MMP-3 que les MCP. Sous l’influence d’un stimulus pro-inflammatoire (IL-1β), l’accroissement de sécrétion de l’IL-6 était 6 fois plus importante aux genoux qu’aux IPP, celui de la MMP-3 plus important aux IPP qu’aux MCP et qu’aux genoux. Les cartilages arthrosiques stimulés par l’IL-1β montraient des accroissements de sécrétion de l’IL-6 et de la PGE2 plus importants aux genoux qu’aux IPP. Enfin, les taux sériques d’HCit et de CML n’étaient pas corrélés à la sévérité de l’atteinte radiolographique dans une cohorte de patients souffrant d’arthrose des mains. Au total, il existe des différences de composition biochimique, et des différences fonctionnelles biologiques entre les cartilages digitaux et de genoux. Le développement de nouvelles approches thérapeutiques doit prendre en compte cette variabilité

Influence of the anatomical location of cartilage on its composition and biological response to inflammatory stress

L'arthrose de la main est la deuxième localisation d'arthrose symptomatique après le genou. Plusieurs études ont suggéré que les propriétés du cartilage dépendaient de sa localisation anatomique. Nous avons comparé des cartilages d’articulations inter-phalangiennes proximales (IPP), métacarpo-phalangiennes (MCP) et de genoux issus de donneurs humains récemment décédés. La densité cellulaire était inversement corrélée à l’épaisseur du cartilage considéré. Les taux d’homocitrulline (HCit) et de carboxymethyllysine (CML), modifications post-traductionnelles des protéines liées au vieillissement, variaient suivant la localisation anatomique. Les cartilages non arthrosiques avaient des profils de sécrétion de base différents selon leur localisation: les IPP sécrétaient moins de MMP-3 que les MCP. Sous l’influence d’un stimulus pro-inflammatoire (IL-1β), l’accroissement de sécrétion de l’IL-6 était 6 fois plus importante aux genoux qu’aux IPP, celui de la MMP-3 plus important aux IPP qu’aux MCP et qu’aux genoux. Les cartilages arthrosiques stimulés par l’IL-1β montraient des accroissements de sécrétion de l’IL-6 et de la PGE2 plus importants aux genoux qu’aux IPP. Enfin, les taux sériques d’HCit et de CML n’étaient pas corrélés à la sévérité de l’atteinte radiolographique dans une cohorte de patients souffrant d’arthrose des mains. Au total, il existe des différences de composition biochimique, et des différences fonctionnelles biologiques entre les cartilages digitaux et de genoux. Le développement de nouvelles approches thérapeutiques doit prendre en compte cette variabilité.Osteoarthritis of the hand is the second most common location of symptomatic osteoarthritis after the knee. Several studies have suggested that the properties of cartilage depend on its anatomical location. We compared cartilage from proximal interphalangeal (PPI), metacarpophalangeal (MCP) and knee joints from recently deceased human donors. Cell density was inversely correlated with cartilage thickness. The levels of homocitrulline (HCit) and carboxymethyllysine (CML), post-translational modifications of proteins related to ageing, varied according to anatomical location. Non-arthritic cartilages had different baseline secretion profiles depending on their location: PPIs secreted less MMP-3 than PCMs. Under the influence of a pro-inflammatory stimulus (IL-1β), the increase in IL-6 secretion was 6-fold greater in knees than in PPIs, that of MMP-3 greater in PPIs than in PCMs and knees. IL-1β-stimulated OA cartilage showed greater increases in IL-6 and PGE2 secretion at the knees than at the PPIs. Finally, serum HCit and CML levels did not correlate with the severity of radiographic damage in a cohort of patients with hand OA. Overall, there are differences in biochemical composition, and biological functional differences between digital and knee cartilage. The development of new therapeutic approaches must take this variability into account

Salvage of an osteocutaneous thermonecrosis secondary to tibial reaming by the induced membrane procedure

Osteocutaneous thermonecrosis is a rare but devastating complication of tibial reaming, which can cause large and infected bone and cutaneous defects. The case presented here illustrates that the induced membrane technique described by Masquelet is a valuable option in treating this complication

Bipolar transfer of the pectoralis major muscle for restoration of elbow

International audienceBACKGROUND:This study evaluated the functional outcomes of bipolar pedicled pectoralis major (PM) transfer to restore elbow flexion.METHODS:We retrospectively reviewed 29 transfers in 28 patients with a mean age of 31.2 years (range, 5-65 years). The loss of elbow flexion was due to brachial plexus palsy in 24 patients, elbow flexors necrosis in 4, and poliomyelitis in 1. The entire PM muscle was mobilized and fixed proximally to the coracoid process. Intraoperative positioning and postoperative immobilization of the shoulder and the elbow flexed at 60° and 120°, respectively, allowed direct distal fixation of the muscle to the biceps brachii tendon.RESULTS:At the last follow-up (mean, 13 months; range, 4-37 months), 41% of the transfers (n = 12) recovered grade 4 elbow flexion strength and were able to lift 2.2 kg on average (range, 0.5-5 kg), 52% (n = 15) recovered grade 3 strength, and 7% (n = 2) had a poor result (ie, grade 2 elbow flexion). The mean active elbow flexion was 100° (ranging, 30°-150°), and the patients had 0° to 10° elbow flexion contracture.CONCLUSIONS:Our results indicate that bipolar PM transfer is a reliable and effective procedure to restore elbow flexion. Flexion of the shoulder and elbow allowed the transfer to reach the elbow fold and avoided an interposition graft between the distal PM and the biceps brachii tendon

Arthrodesis Versus Carpometacarpal Preservation in Key-Grip Procedures in Tetraplegic Patients: A Comparative Study of 40 Cases

International audiencePURPOSE:Constructing a lateral key pinch (KP) is a universal aim of any functional upper limb surgery program for tetraplegia. Three stages are required: (1) activating the pinch mechanism by flexor pollicis longus tenodesis to the radius or by tendon transfer to the flexor pollicis longus, (2) simplifying the polyarticular chain, and (3) positioning the thumb column. We compared 2 techniques for accomplishing the latter stage, 1 utilizing arthrodesis of the carpometacarpal joint (CMC) and 1 that did not require arthrodesis of the CMC.MATERIALS AND METHODS:We reviewed 40 cases of KP reconstruction at a mean follow-up of 7.4 years: 17 who had undergone CMC arthrodesis and 23 without CMC arthrodesis. In this group, an abductor pollicis longus tenodesis was necessary to properly position the thumb column in 17 patients.RESULTS:Active KP cases with CMC arthrodesis were significantly stronger than those without an arthrodesis. For passive KP cases, the difference between those cases with CMC arthrodesis and those without was not significant. Regarding opening, for active KP cases with CMC preservation alone, the mean distance between the thumb pulp and the index finger was 4.0 cm at rest and 5.8 cm when passively grasping large objects; for active KP cases without arthrodesis, these values were 3.4 and 6.8 cm, respectively, with the wrist in flexion. For passive KP cases, these values were 2.2 and 3.5 cm with CMC arthrodesis compared with 2.4 and 6.9 cm without arthrodesis. Overall, 23.5% of patients with CMC arthrodesis could not maintain contact between the thumb and the index finger compared with 30.4% without arthrodesis.CONCLUSIONS:Active KP is stronger with than without CMC arthrodesis; however, the KP reconstruction does not open as far when grasping large objects. For passive KP, CMC arthrodesis significantly limits passive opening, with no gain in strength. Neither technique is superior in terms of KP stability.TYPE OF STUDY/LEVEL OF EVIDENCE:Therapeutic IV

Clearing method for 3-dimensional immunofluorescence of osteoarthritic subchondral human bone reveals peripheral cholinergic nerves

International audienceThe cholinergic system plays a major anti-inflammatory role in many diseases through acetylcholine (Ach) release after vagus nerve stimulation. Osteoarthritis (OA) is associated with local low-grade inflammation, but the regulatory mechanisms are unclear. Local Ach release could have anti-inflammatory activity since articular cells express Ach receptors involved in inflammatory responses. Using the 3DISCO clearing protocol that allows whole-sample 3-dimensional (3D) analysis, we cleared human OA cartilage-subchondral bone samples to search for cholinergic nerve fibres able to produce Ach locally. We analysed 3 plugs of knee cartilage and subchondral bone from 3 OA patients undergoing arthroplasty. We found no nerves in the superficial and intermediate articular cartilage layers, as evidenced by the lack of Peripherin staining (a peripheral nerves marker). Conversely, peripheral nerves were found in the deepest layer of cartilage and in subchondral bone. Some nerves in the subchondral bone samples were cholinergic because they coexpressed peripherin and choline acetyltransferase (ChAT), a specific marker of cholinergic nerves. However, no cholinergic nerves were found in the cartilage layers. It is therefore feasible to clear human bone to perform 3D immunofluorescence. Human OA subchondral bone is innervated by cholinergic fibres, which may regulate local inflammation through local Ach release

Ischemia is the prime but not the only cause of hMSC death in tissue engineered constructs in vivo

International audienceLocal tissue ischemia is a prime cause responsible for the massive cell death in tissue engineered (TE) constructs observed post-implantation. In order to assess the impact of ischemia on the death of implanted human multipotent stromal cells (hMSCs), which have great potential for repairing damaged tissues, we hereby investigated the in vivo temporal and spatial fate of human Luc-GFP-labeled MSCs within fibrin gel/coral scaffolds subcutaneously implanted in nude mice. In vivo bioluminescence imaging monitoring and histological analyses of the constructs tested confirmed the irremediable death of hMSCs over 30 days post-implantation. The kinetics of expression of three hypoxic/ischemic markers (HIF-1α, LDH-A and BNIP3) was also monitored. Our results provided evidence that hMSC located within the core of implanted constructs died faster and predominantly as well as strongly expressed the aforementioned ischemic markers. In contrast, cells located in the outer regions of TE constructs were reperfused by neovascularization and were still viable (as evidenced by their ex-vivo proliferative potential) at day 15 post-implantation. These results support the explanation that in the central part of the constructs tested, death of hMSC cells was due to ischemia, whereas in the periphery of these constructs, cell death was due to another mechanism that needs to be elucidated