Mechanosensory Function Research Articles

Morphology and distribution of ovipositor sensilla of female cotton leaf worm Spodoptera littoralis (Lepidoptera: Noctuidae), and evidence for gustatory function

AbstractThe ovipositor of Spodoptera littoralis has many sensilla, which implies a distinct sensory function of this organ in the assessment of the egg laying substrates and placement of eggs. The ovipositor is composed of two papillae densely packed with sensilla. Scanning electron microscopy showed that there are four categories of sensilla chaetica (s. chaetica), characterized based on differences in distribution, length and morphology, distributed on each papilla: Type I with 69 ± 2.9 sensilla on each papilla (length: 29–163 μm) distributed at the base; Type II with 19 ± 1.8 sensilla (length: 287–446 μm) distributed medially; Type III with 120 ± 7.8 sensilla (length: 62–156 μm) distributed distally; and Type IV 8 ± 0.9 sensilla (length: 72–91 μm) scattered between Type III sensilla. The structure of s. chaetica Types I–III suggests a mechanosensory function, whereas electrophysiological analysis of s. chaetica Type IV showed responses from four gustatory neurons and one mechanosensory neuron. Of the chemoreceptive neurons, one responded to salt, one to the secondary compound caffeine, one to sugars, mainly sucrose and fructose, and lastly one potentially to water. Behavioral studies are needed to verify the role of these sensilla during choice of oviposition site.

Adhesion GPCRs as a Putative Class of Metabotropic Mechanosensors.

Adhesion GPCRs as mechanosensors. Different aGPCR homologs and their cognate ligands have been described in settings, which suggest that they function in a mechanosensory capacity. For details, see text G protein-coupled receptors (GPCRs) constitute the most versatile superfamily of biosensors. This group of receptors is formed by hundreds of GPCRs, each of which is tuned to the perception of a specific set of stimuli a cell may encounter emanating from the outside world or from internal sources. Most GPCRs are receptive for chemical compounds such as peptides, proteins, lipids, nucleotides, sugars, and other organic compounds, and this capacity is utilized in several sensory organs to initiate visual, olfactory, gustatory, or endocrine signals. In contrast, GPCRs have only anecdotally been implicated in the perception of mechanical stimuli. Recent studies, however, show that the family of adhesion GPCRs (aGPCRs), which represents a large panel of over 30 homologs within the GPCR superfamily, displays molecular design and expression patterns that are compatible with receptivity toward mechanical cues (Fig. 1). Here, we review physiological and molecular principles of established mechanosensors, discuss their relevance for current research of the mechanosensory function of aGPCRs, and survey the current state of knowledge on aGPCRs as mechanosensing molecules.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Induced Dyspepsia.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed group of drugs in the world. They are used primarily for pain relief in chronic inflammatory joint disease and act by inhibiting enzymes COX1 and COX2 and ultimately preventing the production of active prostanoids which are required for the innate inflammatory pathway. The use of NSAIDs have been associated with the development of gastrointestinal (GI) symptoms ranging from simple dyspepsia to life threatening GI bleeds and perforations. The definition of dyspepsia has evolved over the years and this has hampered accurate studies on the prevalence of dyspepsia as different studies used varying criteria to define dyspepsia. It is now known that NSAIDs significantly increase the risk of dyspepsia.The risk of developing peptic ulcer disease vary with specific NSAIDs and dosages but there is no correlation between the symptoms of dyspepsia and underlying peptic ulcers. The pathogenesis of dyspepsia with NSAIDs is not completely understood. Peptic ulceration alone is not able to account for the majority of dyspepsia symptoms encountered by NSAIDs users. Erosive oesophagitis secondary to NSAIDs may be contributing factor to the prevalence of dyspepsia in NSAIDs users. Altered gut permeability and changes in gastric mechanosensory function due to NSAIDs may also be a contributory factor. Management of NSAID induced dyspepsia is involves a multipronged approach. Drug avoidance if possible would be ideal. Other options include using the lowest effective dose, changing to an NSAIDs with a safer GI risk profile, avoiding concurrent use with other NSAIDs or if the patient has a previous history of peptic ulcer disease, and co-prescribing with anti-secretory medications such as proton pump inhibitors. Eradication of Helicobacter pylori has a protective role against developing peptic ulcers and may also improve symptoms of NSAIDs induced dyspepsia.

Micro-anatomical and functional assessment of ciliated epithelium in mouse trachea using optical coherence phase microscopy.

Motile cilia perform a range of important mechanosensory and chemosensory functions, along with expulsion of mucus and inhaled pathogens from the lungs. Here we demonstrate that spectral domain optical coherence phase microscopy (SD-OCPM), which combines the principles of optical coherence tomography (OCT) and confocal microscopy, is particularly well-suited for characterization of both morphology and the ciliary dynamics of mouse trachea. We present micro-anatomical images of mouse trachea, where different cell types can be clearly visualized. The phase contrast, which measures the sub-nanometer changes in axial optical pathlength is used to determine the frequency and direction of cilia beatings.

Metamorphic changes in abdominal spines of Forcipomyia nigra pupae (Diptera: Ceratopogonidae)

Pupae of Forcipomyia nigra biting midges bear double rows of dorsal and lateral spines. Their arrangement corresponds to the distribution of larval mechanosensory setae. They are serrated simple cuticular structures with tubercles but, in contrast to larval secretory mechanoreceptors, they are not innervated and do not exhibit any pores. The ultrastructure of abdominal spines varies among different pupal stages. They are produced by epidermal cells which fill the interior of the spine. In the youngest pupae epidermal cells are tightly packed and adhere to the cuticle. Then, the cells withdraw from the spinal cavity and the beginning of autophagy is observed. The last stage represents abdominal spines without any cellular material and then apoptosis probably proceeds in the withdrawn epidermal cells. Since the pupal spines occupied the same region of the segment as the larval setae, we consider that the same genes are responsible for their formation as for the formation of epidermal cells but that their mechanosensory and secretory function is no longer needed.

Functional role of the transient receptor potential melastatin 8 (TRPM8) ion channel in the urinary bladder assessed by conscious cystometry and ex vivo measurements of single‐unit mechanosensitive bladder afferent activities in the rat

To evaluate the role of the transient receptor potential melastatin 8 (TRPM8) channel on bladder mechanosensory function by using L-menthol, a TRPM8 agonist, and RQ-00203078 (RQ), a selective TRPM8 antagonist. Female Sprague-Dawley rats were used. In conscious cystometry (CMG), the effects of intravesical instillation of L-menthol (3 mm) were recorded after intravenous (i.v.) pretreatment with RQ (3 mg/kg) or vehicle. The direct effects of RQ on conscious CMG and deep body temperature were evaluated with cumulative i.v. administrations of RQ at 0.3, 1, and 3mg/kg. Single-unit mechanosensitive bladder afferent activities (SAAs) were monitored in a newly established ex vivo rat bladder model to avoid systemic influences of the drugs. Recordings were performed after cumulative intra-aortic administration of RQ (0.3 and 3 mg/kg) with or without intra-vesical L-menthol instillation (3 mm). Intravesical L-menthol decreased bladder capacity and voided volume, which was counteracted by RQ-pretreatment. RQ itself increased bladder capacity and voided volume, and lowered deep body temperature in a dose-dependent manner. RQ decreased mechanosensitive SAAs of C-fibres, and inhibited the activation of SAAs induced by intravesical L-menthol. Our results suggest that TRPM8 channels have a role in activation of bladder afferent pathways during filling of the bladder in the normal rat. This effect seems, at least partly, to be mediated via mechanosensitive C-fibres.

Synaptic-like vesicles and candidate transduction channels in mechanosensory terminals.

This article summarises progress to date over an exciting and very enjoyable first 15 years of collaboration with Bob Banks. Our collaboration began when I contacted him with (to me) an unexpected observation that a dye used to mark recycling synaptic vesicle membrane at efferent terminals also labelled muscle spindle afferent terminals. This observation led to the re-discovery of a system of small clear vesicles present in all vertebrate primary mechanosensory nerve terminals. These synaptic-like vesicles (SLVs) have been, and continue to be, the major focus of our work. This article describes our characterisation of the properties and functional significance of these SLVs, combining our complementary skills: Bob’s technical expertise and encyclopaedic knowledge of mechanosensation with my experience of synaptic vesicles and the development of the styryl pyridinium dyes, of which the most widely used is FM1-43. On the way we have found that SLVs seem to be part of a constitutive glutamate secretory system necessary to maintain the stretch-sensitivity of spindle endings. The glutamate activates a highly unusual glutamate receptor linked to phospholipase D activation, which we have termed the PLD-mGluR. It has a totally distinct pharmacology first described in the hippocampus nearly 20 years ago but, like the SLVs that were first described over 50 years ago, has since been little researched. Yet, our evidence and literature searches suggest this glutamate/SLV/PLD-mGluR system is a ubiquitous feature of mechanosensory endings and, at least for spindles, is essential for maintaining mechanosensory function. This article summarises how this system integrates with the classical model of mechanosensitive channels in spindles and other mechanosensory nerve terminals, including hair follicle afferents and baroreceptors controlling blood pressure. Finally, in this time when there is an imperative to show translational relevance, I describe how this fascinating system might actually be a useful therapeutic drug target for clinical conditions such as hypertension and muscle spasticity. This has been a fascinating 15-year journey in collaboration with Bob who, as well as having an astute scientific mind, is also a great enthusiast, motivator and friend. I hope this exciting and enjoyable journey will continue well into the future.

The Drosophila homologue of Rootletin is required for mechanosensory function and ciliary rootlet formation in chordotonal sensory neurons.

BackgroundIn vertebrates, rootletin is the major structural component of the ciliary rootlet and is also part of the tether linking the centrioles of the centrosome. Various functions have been ascribed to the rootlet, including maintenance of ciliary integrity through anchoring and facilitation of transport to the cilium or at the base of the cilium. In Drosophila, Rootletin function has not been explored.ResultsIn the Drosophila embryo, Rootletin is expressed exclusively in cell lineages of type I sensory neurons, the only somatic cells bearing a cilium. Expression is strongest in mechanosensory chordotonal neurons. Knock-down of Rootletin results in loss of ciliary rootlet in these neurons and severe disruption of their sensory function. However, the sensory cilium appears largely normal in structure and in localisation of proteins suggesting no strong defect in ciliogenesis. No evidence was found for a defect in cell division.ConclusionsThe role of Rootletin as a component of the ciliary rootlet is conserved in Drosophila. In contrast, lack of a general role in cell division is consistent with lack of centriole tethering during the centrosome cycle in Drosophila. Although our evidence is consistent with an anchoring role for the rootlet, severe loss of mechanosensory function of chordotonal (Ch) neurons upon Rootletin knock-down may suggest a direct role for the rootlet in the mechanotransduction mechanism itself.

Drosophila Hook-Related Protein (Girdin) Is Essential for Sensory Dendrite Formation.

The dendrite of the sensory neuron is surrounded by support cells and is composed of two specialized compartments: the inner segment and the sensory cilium. How the sensory dendrite is formed and maintained is not well understood. Hook-related proteins (HkRP) like Girdin, DAPLE, and Gipie are actin-binding proteins, implicated in actin organization and in cell motility. Here, we show that the Drosophila melanogaster single member of the Hook-related protein family, Girdin, is essential for sensory dendrite formation and function. Mutations in girdin were identified during a screen for fly mutants with no mechanosensory function. Physiological, morphological, and ultrastructural studies of girdin mutant flies indicate that the mechanosensory neurons innervating external sensory organs (bristles) initially form a ciliated dendrite that degenerates shortly after, followed by the clustering of their cell bodies. Importantly, we observed that Girdin is expressed transiently during dendrite morphogenesis in three previously unidentified actin-based structures surrounding the inner segment tip and the sensory cilium. These actin structures are largely missing in girdin mutant. Defects in cilia are observed in other sensory organs such as those mediating olfaction and taste, suggesting that Girdin has a general role in forming sensory dendrites in Drosophila. These suggest that Girdin functions temporarily within the sensory organ and that this function is essential for the formation of the sensory dendrites via actin structures.

Complex impairment of IA muscle proprioceptors following traumatic or neurotoxic injury.

The health of primary sensory afferents supplying muscle has to be a first consideration in assessing deficits in proprioception and related motor functions. Here we discuss the role of a particular proprioceptor, the IA muscle spindle proprioceptor in causing movement disorders in response to either regeneration of a sectioned peripheral nerve or damage from neurotoxic chemotherapy. For each condition, there is a single preferred and widely repeated explanation for disability of movements associated with proprioceptive function. We present a mix of published and preliminary findings from our laboratory, largely from invivo electrophysiological study of treated rats to demonstrate newly discovered IA afferent defects that seem likely to make important contributions to movement disorders. First, we argue that reconnection of regenerated IA afferents with inappropriate targets, although often repeated as the reason for lost stretch-reflex contraction, is not a complete explanation. We present evidence that despite successful recovery of stretch-evoked sensory signaling, peripherally regenerated IA afferents retract synapses made with motoneurons in the spinal cord. Second, we point to evidence that movement disability suffered by human subjects months after discontinuation of oxaliplatin (OX) chemotherapy for some is not accompanied by peripheral neuropathy, which is the acknowledged primary cause of disability. Our studies of OX-treated rats suggest a novel additional explanation in showing the loss of sustained repetitive firing of IA afferents during static muscle stretch. Newly extended investigation reproduces this effect in normal rats with drugs that block Na(+) channels apparently involved in encoding static IA afferent firing. Overall, these findings highlight multiplicity in IA afferent deficits that must be taken into account in understanding proprioceptive disability, and that present new avenues and possible advantages for developing effective treatment. Extending the study of IA afferent deficits yielded the additional benefit of elucidating normal processes in IA afferent mechanosensory function.

γEpithelial Na(+) Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1) expression in the urothelium of patients with neurogenic detrusor overactivity.

To investigate the expression of two types of cation channels, γEpithelial Na(+) Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1), in the urothelium of controls and in patients affected by neurogenic detrusor overactivity (NDO). In parallel, urodynamic parameters were collected and correlated to the immunohistochemical results. Four controls and 12 patients with a clinical diagnosis of NDO and suprasacral spinal cord lesion underwent urodynamic measurements and cystoscopy. Cold-cup biopsies were frozen and processed for immunohistochemistry and Western Blot. Spearman's correlation coefficient between morphological and urodynamic data was applied. One-way anova followed by Newman-Keuls multiple comparison post hoc test was applied for Western Blot results. In the controls, γENaC and ASIC1 were expressed in the urothelium with differences in their cell distribution and intensity. In patients with NDO, both markers showed consistent changes either in cell distribution and labelling intensity compared with the controls. A significant correlation between a higher intensity of γENaC expression in the urothelium of patients with NDO and lower values of bladder compliance was detected. The present findings show important changes in the expression of γENaC and ASIC1 in NDO human urothelium. Notably, while the changes in γENaC might impair the mechanosensory function of the urothelium, the increase of ASIC1 might represent an attempt to compensate for the excess in local sensitivity.

Dopaminergic signaling within the primary cilia in the renovascular system.

Activation of dopamine receptor type-5 (DR5) has been known to reduce systemic blood pressure, most likely by increasing renal vasodilation and enhancing natriuresis in the kidney. However, the mechanism of DR5 in natriuresis and vasodilation was not clearly known. We have previously shown that DR5 is localized to primary cilia of proximal renal epithelial and vascular endothelial cells. We here show that selective activation of DR5 specifically induces calcium influx only in the primary cilia, whereas non-selective activation of dopamine receptor induces calcium fluxes in both cilioplasm and cytoplasm. Cilia-independent signaling induced by thrombin only shows calcium signaling within cytoplasm. Furthermore, calcium activation in the cilioplasm by DR5 increases length and mechanosensory function of primary cilia, leading to a greater response to fluid-shear stress. We therefore propose a new mechanism by which DR5 induces vasodilation via chemical and mechanical properties that are specific to primary cilia.

Alaskan Botanicals Influence Neuronal Aging

Aging is a risk factor for many life‐threatening disorders, including neurodegenerative diseases. Many genetic mutations and environmental factors that increase lifespan may also postpone these age‐related diseases. The overall goal of this project is to examine the effect of Alaskan botanicals on the aging nervous system, using the nematode model system, Caenorhabditis elegans. We tested the impact of crude extracts from three edible, medicinally beneficial Interior Alaskan botanicals (Vaccinium uliginosum [bog blueberry], Empetrum nigrum [crowberry], Vaccinium vitis‐idaea [lowbush cranberry], Inonotus obliquus [chaga]) on whole animal lifespan and markers of neuronal aging. Specifically, we evaluated age‐ and botanical‐related changes in neuronal morphology and function of mechanosensory and GABAergic motor neurons using fluorescently labeled C. elegans strains. We find that these botanicals are able to extend wildtype C. elegans lifespan by up to 35%. Preliminary results suggest that mechanosensory neuronal morphology and function are also affected, but not GABA‐ergic neurons. We explored the mechanism of action of these botanicals through determining the extracts' phenolic, flavonoid, and anthocyanin composition and in vivo DAF‐16, SKN‐1, and HSF‐1 transcription factor activation following treatments. Through this botanical screen, we will scientifically validate and underscore the value of ecological resources endemic to the Arctic, elucidate the mechanism of changing neuronal morphology and functionality with age, and, perhaps, establish precedent for novel therapies for neurodegenerative diseases.

Expression of prestin in OHCs is reduced in Spag6 gene knockout mice

Sperm-associated antigen 6 (Spag6) gene, which encodes an axonemal protein (SPAG6), ubiquitously expresses in tissue and organs containing ciliated cells. The present work was to investigate whether SPAG6 expressed in cochlear hair cells and, if so, to explore the presumable correlations between prestin and SPAG6. The distribution of SPAG6 in organ of Corti and the morphological features of hair cells in basilar membrane were investigated by immunofluorescent staining. The amount of prestin in Spag6 mutant mice was measured by Western blotting and real-time PCR, respectively. Additionally, co-immunoprecipitation tests were performed to confirm the presumed interaction between prestin and SPAG6. We observed that SPAG6 expressed in the cuticular plate in outer hair cells (OHCs) and prestin in the lateral wall of OHCs that located along with SPAG6 at this site. In comparison to Spag6 +/+ mice, Spag6 −/− mice showed apparent morphological abnormity of OHCs and lower intensity of prestin fluorescence. The expression of prestin in Spag6 −/− mice reduced significantly at both protein and mRNA levels. Moreover, co-immunoprecipitation tests demonstrated the interaction between prestin and SPAG6. Taken together, these data indicate that SPAG6 is indispensible for the stability of OHCs by maintaining the normal expression of prestin, which implies that Spag6 gene is essential for mechanosensory function of OHCs.

Control of a hair bundle’s mechanosensory function by its mechanical load

Hair cells, the sensory receptors of the internal ear, subserve different functions in various receptor organs: they detect oscillatory stimuli in the auditory system, but transduce constant and step stimuli in the vestibular and lateral-line systems. We show that a hair cell's function can be controlled experimentally by adjusting its mechanical load. By making bundles from a single organ operate as any of four distinct types of signal detector, we demonstrate that altering only a few key parameters can fundamentally change a sensory cell's role. The motions of a single hair bundle can resemble those of a bundle from the amphibian vestibular system, the reptilian auditory system, or the mammalian auditory system, demonstrating an essential similarity of bundles across species and receptor organs.

The Role of Atonal Factors in Mechanosensory Cell Specification and Function.

Atonal genes are basic helix-loop-helix transcription factors that were first identified as regulating the formation of mechanoreceptors and photoreceptors in Drosophila. Isolation of vertebrate homologs of atonal genes has shown these transcription factors to play diverse roles in the development of neurons and their progenitors, gut epithelial cells, and mechanosensory cells in the inner ear and skin. In this article, we review the molecular function and regulation of atonal genes and their targets, with particular emphasis on the function of Atoh1 in the development, survival, and function of hair cells of the inner ear. We discuss cell-extrinsic signals that induce Atoh1 expression and the transcriptional networks that regulate its expression during development. Finally, we discuss recent work showing how identification of Atoh1 target genes in the cerebellum, spinal cord, and gut can be used to propose candidate Atoh1 targets in tissues such as the inner ear where cell numbers and biochemical material are limiting.

Enhanced axon outgrowth and improved long-distance axon regeneration in sprouty2 deficient mice.

Sprouty (Spry) proteins are negative feedback inhibitors of receptor tyrosine kinase signaling. Downregulation of Spry2 has been demonstrated to promote elongative axon growth of cultured peripheral and central neurons. Here, we analyzed Spry2 global knockout mice with respect to axon outgrowth in vitro and peripheral axon regeneration in vivo. Neurons dissociated from adult Spry2 deficient sensory ganglia revealed stronger extracellular signal-regulated kinase activation and enhanced axon outgrowth. Prominent axon elongation was observed in heterozygous Spry2(+/-) neuron cultures, whereas homozygous Spry2(-/-) neurons predominantly exhibited a branching phenotype. Following sciatic nerve crush, Spry2(+/-) mice recovered faster in motor but not sensory testing paradigms (Spry2(-/-) mice did not tolerate anesthesia required for nerve surgery). We attribute the improvement in the rotarod test to higher numbers of myelinated fibers in the regenerating sciatic nerve, higher densities of motor endplates in hind limb muscles and increased levels of GAP-43 mRNA, a downstream target of extracellular regulated kinase signaling. Conversely, homozygous Spry2(-/-) mice revealed enhanced mechanosensory function (von Frey's test) that was accompanied by an increased innervation of the epidermis, elevated numbers of nonmyelinated axons and more IB4-positive neurons in dorsal root ganglia. The present results corroborate the functional significance of receptor tyrosine kinase signaling inhibitors for axon outgrowth during development and nerve regeneration and propose Spry2 as a novel potential target for pharmacological inhibition to accelerate long-distance axon regeneration in injured peripheral nerves.

Insulin signaling in the aging of healthy and proteotoxically stressed mechanosensory neurons.

Insulin signaling is central to cellular metabolism and organismal aging. However, the role of insulin signaling in natural and proteotoxically stressed aging neurons has yet to be fully described. We studied aging of Caenorbaditis elegans mechanosensory neurons expressing a neurotoxic expanded polyglutamine transgene (polyQ128), or lacking this proteotoxicity stressor (polyQ0), under conditions in which the insulin signaling pathway was disrupted by RNA interference (RNAi). We describe specific changes in lifespan, mechanosensory neuronal morphologies, and mechansensory function following RNAi treatment targeting the insulin signaling pathway. Overall, we confirmed that transcription factor DAF-16 is neuroprotective in the proteotoxically stressed model, though not strikingly in the naturally aging model. Decreased insulin signaling through daf-2 RNAi improved mechanosensory function in both models and decreased protein aggregation load in polyQ128, yet showed opposing effects on accumulation of neuronal aberrations in both strains. Decreased daf-2 signaling slightly enhanced mechanosensation while greatly enhancing branching of the mechanosensory neuron axons and dendrites in polyQ0 animals, suggesting that branching is an adaptive response in natural aging. These effects in polyQ0 did not appear to involve DAF-16, suggesting the existence of a non-canonical DAF-2 pathway for the modulation of morphological adaptation. However, in polyQ128 animals, decreased daf-2 signaling significantly enhanced mechanosensation while decreasing neuronal aberrations. Unlike other interventions that reduce the strength of insulin signaling, daf-2 RNAi dramatically redistributed large polyQ128 aggregates to the cell body, away from neuronal processes. Our results suggest that insulin signaling strength can differentially affect specific neurons aging naturally or under proteotoxic stress.

Merkel cells and touch domes: more than mechanosensory functions?

The touch dome (TD) is an innervated structure in the epidermis of mammalian skin. Composed of specialized keratinocytes and neuroendocrine Merkel cells, the TD has distinct molecular characteristics compared to the surrounding epidermal keratinocytes. Much of the research on Merkel cell function has focused on their role in mechanosensation, specifically light touch. Recently, more has been discovered about Merkel cell molecular characteristics and their cells of origin. Here we review Merkel cell and TD biology, and discuss potential functions beyond mechanosensation.

Function and regulation of primary cilia and intraflagellar transport proteins in the skeleton.

Primary cilia are microtubule-based organelles that project from the cell surface to enable transduction of various developmental signaling pathways. The process of intraflagellar transport (IFT) is crucial for the building and maintenance of primary cilia. Ciliary dysfunction has been found in a range of disorders called ciliopathies, some of which display severe skeletal dysplasias. In recent years, interest has grown in uncovering the function of primary cilia/IFT proteins in bone development, mechanotransduction, and cellular regulation. We summarize recent advances in understanding the function of cilia and IFT proteins in the regulation of cell differentiation in osteoblasts, osteocytes, chondrocytes, and mesenchymal stem cells (MSCs). We also discuss the mechanosensory function of cilia and IFT proteins in bone cells, cilia orientation, and other functions of cilia in chondrocytes.